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60-1108: It is used in patients with parkinsonism and akathisia , and to reduce the side effects of antipsychotic treatment given for schizophrenia . Procyclidine is also a second-line drug for the treatment of Parkinson's disease . It improves tremor but not rigidity or bradykinesia . Procyclidine is also sometimes used for the treatment of dystonia (but not tardive dyskinesia ), a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face. Side effects include nausea, constipation, urinary retention, blurred vision, anxiety, cognitive impairment, confusion, dizziness, gingivitis, hallucination, memory loss, rash and vomiting. Signs of procyclidine overdose are those of an anticholinergic and include confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations have also been reported. Other known symptoms of overdose are: clumsiness or unsteadiness, being severely drowsy, having

120-442: A polyglutamine (polyQ) tract . Diseases associated with such mutations are known as trinucleotide repeat disorders . Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ studies often use

180-614: A 99.5% failure rate. Reasons for this failure rate include inappropriate drug doses, invalid target and participant selection, and inadequate knowledge of pathophysiology of AD. Currently, diagnoses of Alzheimer's is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimer's has a 20% misdiagnosis rate. AD pathology is primarily characterized by the presence of amyloid plaques and neurofibrillary tangles . Plaques are made up of small peptides , typically 39–43 amino acids in length, called amyloid beta (also written as A-beta or Aβ). Amyloid beta

240-646: A cause of parkinsonism, although evidence is inconclusive and further research is needed. Other toxins that have been associated with parkinsonism are: Secondary parkinsonism, including vascular parkinsonism and drug-induced parkinsonism. About 7% of people with parkinsonism developed symptoms as a result of side effects of medication, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine ), thioxanthenes (such as flupentixol and zuclopenthixol ) and butyrophenones (such as haloperidol ), and rarely, antidepressants . Yet another drug that can induce parkinsonism

300-430: A conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite

360-451: A fifth of consumed oxygen, and reactive oxygen species produced by oxidative metabolism are a major source of DNA damage in the brain . Damage to a cell's DNA is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with

420-939: A gradual decline in the activities of repair mechanisms , could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia- oculomotor apraxia . Increased oxidative DNA damage in the brain is associated with Alzheimer's disease and Parkinson's disease . Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis , ataxia telangiectasia , Cockayne syndrome , Parkinson's disease and xeroderma pigmentosum . Axonal swelling, and axonal spheroids have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles. Axonal transport can be disrupted by

480-406: A link between exposure to pesticides and herbicides and PD; a two-fold increase in risk was seen with paraquat or maneb / mancozeb exposure. Chronic manganese (Mn) exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities. This condition is not responsive to typical therapies used in the treatment of PD , suggesting an alternative pathway than

540-561: A reaction termed transamidation or crosslinking . Transglutaminase binding of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption. Most relevant human neurodegenerative diseases share the property of having abnormal structures made up of proteins and peptides . Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In Alzheimer's disease , these are amyloid-beta and tau . In Parkinson's disease, it

600-465: A role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. The main known risk factor

660-405: A severely dry mouth, nose, or throat, having an altered mood or other mental changes, seizures, being short of breath or having troubled breathing, a dry and warm, flushed skin. A suspected overdose with severe life-threatening symptoms should immediately be brought to medical attention, where reversal can be attempted with physostigmine administered intravenously or subcutaneously. Procyclidine

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720-399: A spectrum based on the degree of inflammation, a majority of patients experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of multiple sclerosis. The inflammatory response contributes to

780-511: A subset of patients with familial ALS. More recently, TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma (FUS) protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 ( C9orf72 ) is thought to be the most common known cause of sporadic ALS. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there

840-588: A variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the models of nematode ( C. elegans ), and fruit fly ( Drosophila ), mice, and non-human primates. Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including Huntington's disease and the spinocerebellar ataxias . The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example

900-690: A variety of mechanisms including damage to: kinesin and cytoplasmic dynein , microtubules , cargoes, and mitochondria . When axonal transport is severely disrupted a degenerative pathway known as Wallerian-like degeneration is often triggered. Programmed cell death (PCD) is death of a cell in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinson's disease, amytrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic; alternatively, PCD may occur in response to other injury or disease processes. Apoptosis

960-491: Is FKBP5 gene, which progressively increases its expression with age and has been related to Braak staging and increased tau pathology both in vitro and in mouse models of AD. Several neurodegenerative diseases are classified as proteopathies as they are associated with the aggregation of misfolded proteins . Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. Parkinson's disease and Huntington's disease are both late-onset and associated with

1020-777: Is aging . Mitochondrial DNA mutations as well as oxidative stress both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that DNA damage accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing speed. A study using electronic health records indicates that 45 (with 22 of these being replicated with

1080-573: Is alpha-synuclein . In Huntington's disease, it is huntingtin . Transglutaminase substrates : Amyloid-beta , tau , alpha-synuclein and huntingtin have been proved to be substrates of transglutaminases in vitro or in vivo, that is, they can be bonded by trasglutaminases by covalent bonds to each other and potentially to any other transglutaminase substrate in the brain. Transglutaminase augmented expression: It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease)

1140-518: Is a clinical syndrome characterized by the four motor symptoms found in Parkinson's disease : tremor , bradykinesia (slowed movements), rigidity , and postural instability . Parkinsonism gait problems can lead to falls and serious physical injuries. Other common symptoms include: Parkinsonism occurs in many conditions. Neurodegenerative conditions and Parkinson-plus syndromes that can cause parkinsonism include: Evidence exists to show

1200-456: Is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death. Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. There are two types of caspases: initiators and effectors . Initiator caspases cleave inactive forms of effector caspases. This activates

1260-428: Is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is cleaved into smaller fragments by enzymes such as gamma secretase and beta secretase . One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into

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1320-438: Is a rare neurodegenerative disorder characterized by the gradual loss of both upper motor neurons (UMNs) and lower motor neurons (LMNs). Although initial symptoms may vary, most patients develop skeletal muscle weakness that progresses to involve the entire body. The precise etiology of ALS remains unknown. In 1993, missense mutations in the gene encoding the antioxidant enzyme superoxide dismutase 1 (SOD1) were discovered in

1380-479: Is a source of controversy among medical professionals. The gut microbiome might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment. Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the huntingtin gene (HTT) . HD is characterized by loss of medium spiny neurons and astrogliosis . The first brain region to be substantially affected

1440-461: Is age. Mutations in genes such as α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and tau protein (MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinson's disease (PD), however, some neurologists question its efficacy. This assessment method

1500-434: Is an anticholinergic . It is specifically an antimuscarinic . The drug acts as a non-selective antagonist of the muscarinic acetylcholine M 1 , M 2 , and M 4 receptors , whereas its activities at the M 3 and M 5 receptors are reportedly unknown. Procyclidine, 1-cyclohexyl-1-phenyl-3-pyrrolidinopropan-1-ol, is synthesized in exactly the same manner as was seen for trihexyphenidyl , except this time

1560-425: Is characterized by motor impairment, epilepsy , dementia , vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on

1620-400: Is deleterious to the cell and would eventually lead to cell death. Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins. The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from

1680-433: Is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people. The consequences of neurodegeneration can vary widely depending on the specific region affected, ranging from issues related to movement to the development of dementia. Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in

1740-456: Is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause necrosis at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It

1800-608: Is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy ) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. Within neurodegenerative diseases, it

1860-445: Is primarily characterized by death of dopaminergic neurons in the substantia nigra , a region of the midbrain . The cause of this selective cell death is unknown. Notably, alpha-synuclein - ubiquitin complexes and aggregates are observed to accumulate in Lewy bodies within affected neurons. It is thought that defects in protein transport machinery and regulation, such as RAB1 , may play

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1920-502: Is proposed to be due to the release of antigens such as myelin oligodendrocyte glycoprotein , myelin basic protein , and proteolipid protein , causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and macrophages to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as

1980-448: Is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0–32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients. Independent research provided in vitro evidence that

2040-401: Is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis. Transglutaminases are human enzymes ubiquitously present in the human body and in the brain in particular. The main function of transglutaminases is bind proteins and peptides intra- and intermolecularly, by a type of covalent bonds termed isopeptide bonds , in

2100-415: Is the antihistaminic medication cinnarizine , usually prescribed for motion sickness; this is because besides antagonizing histamine receptors this drug antagonizes the dopamine D2 receptors . The incidence of drug-induced parkinsonism increases with age. Drug-induced parkinsonism tends to remain at its presenting level and does not worsen like Parkinson's disease. Implicated medications include: In

2160-449: Is the striatum , followed by degeneration of the frontal and temporal cortices. The striatum's subthalamic nuclei send control signals to the globus pallidus , which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea . Huntington's disease presents itself later in life even though

2220-400: Is the common name for a group of lysosomal storage disorders known as neuronal ceroid lipofuscinoses (NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, NCL3 disease (juvenile NCL) typically manifests between the ages of 4 and 7. Batten disease

2280-500: The UK Biobank ) viral exposures can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection. Many neurodegenerative diseases are caused by genetic mutations , most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid glutamine . A repeat of CAG results in

2340-438: The cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe , parietal lobe , and parts of the frontal cortex and cingulate gyrus . It is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimer's disease, no effective treatments have been found. Within clinical trials stable and effective AD therapeutic strategies have

2400-454: The expression of the transglutaminase enzyme is increased. Presence of isopeptide bonds in these structures: The presence of isopeptide bonds (the result of the transglutaminase reaction) have been detected in the abnormal structures that are characteristic of these neurodegenerative diseases . Co-localization: Co-localization of transglutaminase mediated isopeptide bonds with these abnormal structures has been detected in

2460-573: The mitochondrial intermembrane space . Reactive oxygen species (ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and glutathione peroxidase . Over production of ROS ( oxidative stress ) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, mitochondrial fission and fusion , lipid concentration of

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2520-457: The United States, the 2021 National Defense Authorization Act (NDAA) added parkinsonism to the list of presumptive conditions associated with Agent Orange exposure, enabling affected service members to receive Veterans Affairs disability benefits.   Creutzfeldt–Jakob disease Neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons , in

2580-723: The accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as proteopathies , and they are primarily caused by aggregates in the following structures: There are two main avenues eukaryotic cells use to remove troublesome proteins or organelles: Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles. The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature

2640-502: The autopsy of brains of patients with these diseases. The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures. In the search for effective treatments (as opposed to palliative care ), investigators employ animal models of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show

2700-492: The dense extracellular amyloid plaques. Parkinson's disease (PD) is the second most common neurodegenerative disorder. It typically manifests as bradykinesia , rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. PD

2760-489: The disease. Multiple sclerosis (MS) is a chronic debilitating demyelinating disease of the central nervous system , caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which

2820-410: The effectors that in turn cleave other proteins resulting in apoptotic initiation. Autophagy is a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an autophagosome , which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it

2880-443: The four motor symptoms found in Parkinson's disease (PD) – after which it is named – dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of symptoms occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins , metabolic diseases , and neurological conditions other than PD. Parkinsonism

2940-624: The linear synthesis begins with the preparation of 3-(1-pyrrolidino)propiophenone. In an interesting variation, the ketone is first reacted with phenylmagnesium bromide. Catalytic hydrogenation of the carbinol thus obtained can be stopped after the reduction of only one aromatic ring. Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor , bradykinesia (slowed movements), rigidity , and postural instability . Both hypokinetic (bradykinesia and akinesia) as well as hyperkinetic (cogwheel rigidity and tremors at rest) features are displayed by Parkinsonism. These are

3000-519: The loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the HLA-DRB1*15:01 allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS. Amyotrophic lateral sclerosis (ALS), commonly referred to Lou Gehrig's disease,

3060-714: The mitochondrial membranes, and the mitochondrial permeability transition. Mitochondrial disease leading to neurodegeneration is likely, at least on some level, to involve all of these functions. There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases Alzheimer's , Parkinson's , Huntington's , and amyotrophic lateral sclerosis . Neurons are particularly vulnerable to oxidative damage due to their strong metabolic activity associated with high transcription levels, high oxygen consumption, and weak antioxidant defense. The brain metabolizes as much as

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3120-705: The pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication. In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus amyloid-beta 25–35. This suggests that there could be therapeutic value to PRP-1. Protein degradation offers therapeutic options both in preventing

3180-441: The primary cellular sites where SOD1 mutations act are located on astrocytes . Astrocytes then cause the toxic effects on the motor neurons . The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. Batten disease is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease

3240-471: The process known as neurodegeneration . Neuronal damage may also ultimately result in their death . Neurodegenerative diseases include amyotrophic lateral sclerosis , multiple sclerosis , Parkinson's disease , Alzheimer's disease , Huntington's disease , multiple system atrophy , tauopathies , and prion diseases . Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there

3300-686: The proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment. HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as inclusion bodies in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal axonal transport , leading to impaired transport of important cargoes such as BDNF . Huntington's disease currently has no effective treatments that would modify

3360-507: The research process for methods to treat Batten disease. Creutzfeldt–Jakob disease (CJD) is a prion disease that is characterized by rapidly progressive dementia. Misfolded proteins called prions aggregate in brain tissue leading to nerve cell death. Variant Creutzfeldt–Jakob disease (vCJD) is the infectious form that comes from the meat of a cow that was infected with bovine spongiform encephalopathy , also called mad cow disease. The greatest risk factor for neurodegenerative diseases

3420-550: The synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are only beginning to understand. The goal of immunotherapy is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions; however, more research must be done to prove safety and efficacy in humans. A current therapeutic target for

3480-416: The treatment of Alzheimer's disease is the protease β-secretase , which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent

3540-562: The typical dopaminergic loss within the substantia nigra . Manganese may accumulate in the basal ganglia , leading to the abnormal movements that characterize parkinsonism. A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this parkinsonism-like disease. The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism. Agent Orange may be

3600-498: The value of any specific therapeutic strategies and drugs when attempting to ameliorate disease severity. An example is the drug Dimebon by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimer's disease, and also phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed in

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