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45-503: PC12 may refer to: PC12 cell line PC12 minicomputer Pilatus PC-12 , a civilian aircraft BAP Río Chira (PC 12) , a vessel of the Peruvian Coast Guard [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change

90-546: A family history , from which 5–10 percent can be attributed to a causative risk gene mutation , although harboring one of these mutations may not lead to the disease. As of 2024, around 90 genetic risk variants across 78 genomic loci have been identified with studies employing next-generation sequencing (NGS) to uncover detailed insights into these genetic factors. Notable risk genes include SNCA , LRRK2 , and VPS35 for autosomal dominant inheritance, and PRKN , PINK1 , and DJ1 for autosomal recessive inheritance. LRRK2

135-505: A clear sensorium . It might overlap with other psychiatric symptoms, making the diagnosis challenging. Impulse-control disorders (ICD) can be seen in approximately 19 percent of all patients and, in the context of PD, are grouped along with compulsive behavior and dopamine dysregulation syndrome (DDS) within the broader spectrum of impulsive and compulsive behaviors (ICB). They are characterized by impulsivity and difficulty to control impulsive urges and are positively correlated with

180-738: A direct role in neurodegeneration , while Lewy bodies are thought to serve as an indirect marker of disease progression. A vicious cycle linked to neurodegeneration involves oxidative stress , mitochondria, and neuroimmune function, particularly inflammation . Normal metabolism of dopamine tends to fail, leading to elevated levels of reactive oxygen species (ROS) which is cytotoxic and causes cellular damage to lipids , proteins , DNA , and especially mitochondria. Mitochondrial damage triggers neuroinflammatory responses via damage-associated molecular patterns (DAMPs), resulting in aggregation of neuromelanin , and therefore, fueling further neuroinflammation by activating microglia . Ferroptosis

225-545: A few contributing factors have been identified. Pathophysiology is characterized by progressively expanding nerve cell death originating in substantia nigra , a midbrain region that supplies dopamine to the basal ganglia , a system involved in voluntary motor control . The cause of this cell death is poorly understood but involves alpha-synuclein aggregation into Lewy bodies within the neurons . Other possible factors involve genetic and environmental mechanisms, medications, lifestyle, and previous conditions. Diagnosis

270-485: A major DNA damage -repair signaling kinase , and non-homologous end joining DNA repair pathway. Identifying environmental risk factors and causality is difficult due to the disease's often decade-long prodromal period. Most noteworthy environmental factors include pesticide exposure and contact with heavy metals. In particular, exposure to pesticides such as paraquat , rotenone , benomyl , and mancozeb causes one in five cases, implying an association with

315-632: Is a neurodegenerative disease , mainly of the central nervous system , that affects both the motor and non-motor systems of the body. The symptoms usually emerge slowly, and, as the disease progresses, non-motor symptoms become more common. Usually symptoms include tremors , slowness of movement , rigidity , and difficulty with balance , collectively known as parkinsonism . Parkinson's disease dementia , falls and neuropsychiatric problems such as sleep abnormalities , psychosis , mood swings , or behavioral changes may also arise in advanced stages. Most cases of Parkinson's disease are sporadic , but

360-413: Is associated with higher morbidity and mortality. Other autonomic-related symptoms include excessive sweating, urinary incontinence , and sexual dysfunction . Neuropsychiatric symptoms (NPS) are common and range from mild disturbances to severe impairment, comprising abnormalities in cognition, mood, behavior, or thought which can interfere with daily activities, reduce quality of life, and increase

405-403: Is caused by a distinct biomechanical process or if it is the manifestation of another cardinal sign of PD. Postural instability (PI) is typical in the later stages of the disease, leading to impaired balance and falls , and secondarily to bone fractures, thus, reduced mobility and quality of life. PI is absent in the initial stages and usually occurs 10–15 years after first diagnosis. Within

450-504: Is considered one of the primary contributing factors for nigrostriatal neuron death in PD. When overexpressed or misfolded , it can form clumps on axon terminals and other neuronal structures, particularly its typical locations: the cytoplasm , mitochondria and nucleus . These aggregates eventually lead to the formation of Lewy bodies . Their precursors, known as oligomers , along with initial deposits called pale bodies, are believed to play

495-498: Is estimated to be responsible for 1-2% of all cases of PD and 40% of familial cases. Additionally, mutations in the GBA1 gene, linked to Gaucher's disease , are found in 5–10 percent of PD cases. The GBA1 variant of genetic PD more commonly involves cognitive decline. Alpha-synuclein (aSyn), a protein encoded by SNCA gene , is thought to be primarily responsible Lewy body aggregation. ASyn activates ATM serine/threonine kinase ,

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540-961: Is known to be present in up to 55 percent of PD patients. While it is responsible for most of paresthesia and pain in Parkingson Disease, its role in postural instability and motor impairment is poorly understood. Alterations in the autonomic nervous system , known as dysautonomia , are associated with a variety of symptoms such as gastrointestinal dysfunction , orthostatic hypotension , excessive sweating, or urinary incontinence. Gastrointestinal issues include constipation, impaired stomach emptying , immoderate production of saliva , and swallowing difficulty (prevalence up to 82 percent). Complications resulting from dysphagia include dehydration , malnutrition, weight loss, and aspiration pneumonia . All gastrointestinal features can be severe enough to cause discomfort, endanger health, and complicate disease management. Despite being related to each other,

585-516: Is mainly based on signs and symptoms , usually motor-related, found via neurological examination , though medical imaging like neuromelanin MRI can support the diagnosis. Usual onset is in people over 60 years of age, of whom about one percent are affected. In those younger than 50, it is termed "early-onset PD". No cure is known; treatment aims to lessen symptoms. Initial treatment typically includes L-DOPA , MAO-B inhibitors , or dopamine agonists . As

630-461: Is near-normal. Parkinson's disease (PD) is a neurodegenerative disease affecting both the central and peripheral nervous systems , characterized by the loss of dopamine -producing neurons in the substantia nigra region of the brain. It is classified as a synucleinopathy due to the abnormal accumulation of the protein alpha-synuclein , which aggregates into Lewy bodies within affected neurons. The loss of dopamine-producing neurons in

675-517: Is referring to releasing neurotransmitter by vesicles. PC12 cells stop dividing and terminally differentiate when treated with nerve growth factor or dexamethasone . This makes PC12 cells useful as a model system for neuronal differentiation and neurosecretion. Treatment of PC12 cells with nerve growth factor creates cells with long processes known as neurite varicosities, which contain small amounts of vesicles. PC12 cells treated for 10–14 days with nerve growth factor had no release of vesicles from

720-428: Is the most common presenting sign and may appear at rest as well as during intentional movement with a frequency between 4–6  hertz (cycles per second). PD tremor tends to occur in the hands, but can affect other parts of the body, such as legs, arms, tongue, or lips, as well. It is often described as " pill-rolling ", the tendency of the index finger and thumb to touch and perform a circular movement that reminds of

765-669: The autonomic or sensory nervous system, mood , behavior, sleep patterns, and cognition. Non-motor symptoms may precede the onset of motor symptoms by up to 20 years. These include constipation, anosmia , mood disorders , and REM sleep behavior disorder among others. In general, motor symptoms such as postural instability and gait abnormalities tend to appear as the disease progresses. Four motor symptoms are considered as cardinal signs in PD: tremor, bradykinesia, rigidity, and postural instability, collectively known as parkinsonism . However, other motor-associated symptoms are common. Tremor

810-590: The dopaminergic system which plays a central role in motor control . Three major pathways connect the basal ganglia to other brain areas: direct, indirect, and hyperdirect pathway, all part of the cortico-basal ganglia-thalamo-cortical loop . The direct pathway projects from the neocortex to putamen or caudate nucleus of the striatum, which sends inhibitory GABAergic signals to substantia nigra pars reticulata (SNpr) and internal globus pallidus (GPi). This inhibition reduces GABAergic signaling to ventral lateral (VL) and ventral anterior (VA) nuclei of

855-478: The thalamus , thereby promoting their projections to the motor cortex . The indirect pathway projects inhibition from striatum to external globus pallidus (GPe), reducing its GABAergic inhibition of the subthalamic nucleus , pars reticulata and internal globus pallidus. This reduction in inhibition allows the subthalamic nucleus to excite internal globus pallidus and pars reticulata, which in turn inhibit thalamic activity, thereby suppressing excitatory signals to

900-557: The cell body which indicates the aggregation of vesicles in the ends of the neurites. Treatment of PC12 cells with dexamethasone differentiates them into chromaffin-like cells. Using patch clamp recording and amperometry , there was a significant increase in quantal size, excitability and coupling between calcium channels and vesicle release sites, increasing from ~2x10 to ~6.5x10 moles. Research has shown differences in vesicle size and quantal size depending on treatment with certain drugs. PC12 cells have been researched to evaluate

945-451: The characteristic reduced facial expression known as "masked face" or hypomimia . Rigidity , also referred to as rigor or "stiffness", is the increased resistance during passive mobilization of a limb affecting up to 89 percent of cases. It usually occurs after onset of tremor and bradykinesia on one or both sides of the body and can lead to muscle or joint pain as the disease progresses. As of 2024, it remains unclear whether rigidity

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990-478: The disease progresses, these medications become less effective and produce a side effect marked by involuntary muscle movements . Diet and certain forms of rehabilitation have shown some effectiveness at improving symptoms. Deep brain stimulation has been used to reduce severe motor symptoms when drugs are ineffective. There is little evidence for treatment of the non-movement-related symptoms, such as sleep disturbances and mood instability. The average life expectancy

1035-404: The disease. Neuronal cell death has been linked to numerous mechanisms, with the most prominent being the misfolding and aggregation of alpha-synuclein , oxidative stress , neuroinflammation , ferroptosis , mitochondrial dysfunction , and gut dysbiosis. Alpha-synuclein (aSyn), a protein involved in synaptic vesicle trafficking , intracellular transport , and neurotransmitter release ,

1080-610: The early pharmaceutical technique of manually making pills. Despite it being the most noticeable sign, tremor is present in only about 70–90 percent of cases. Bradykinesia is often considered the most important feature of Parkinson's disease and is also present in atypical parkinsonism. It describes difficulties in motor planning , beginning, and executing, resulting in overall slowed movement with reduced amplitude which affects sequential and simultaneous tasks. Hence, it interferes with daily activities such as dressing, feeding and bathing. Facial muscles involved in bradykinesia lead to

1125-470: The exact mechanism of these symptoms remains unknown. Orthostatic hypotension is the sustained drop of blood pressure by at least 20 mmHg systolic or 10 mmHg diastolic within the first three minutes after raising to an upright position that can be seen in 30–50 percent of cases. Low blood pressure can impair the perfusion of organs situated above the heart, particularly the brain, resulting in lightheadedness . This can eventually lead to fainting and

1170-456: The exact neurobiological mechanism, and therefore possible connections with other symptoms, remains unknown. Transformation of the sensory nervous system can lead to changes in sensation that include an impaired sense of smell , disturbed vision , pain, and paresthesia . Problems with visuospatial function may arise and lead to difficulties in facial recognition and perception of the orientation of drawn lines. Peripheral neuropathy

1215-409: The first three years after disease onset, PI may indicate atypical parkinsonism. Together with bradykinesia and rigidity, it is responsible for the typical gait characterized by short shuffling steps and forward-flexed posture . Other common motor signs include a slurred and quiet voice, and handwriting that progressively becomes smaller . This latter may occur prior to other typical symptoms, but

1260-400: The function of proteins underlying vesicle fusion . This cell line has been used to understand the role of synaptotagmin in vesicle-cell membrane fusion. Their embryological origin with neuroblastic cells means they can easily differentiate into neuron-like cells even though they are not considered adult neurons. Neuron-like means they share properties similar to neurons, in this case it

1305-408: The general population. Apathy is characterized by emotional indifference and arises in about 46 percent of cases. Diagnosis is difficult, as it may become indistinct from symptoms of depression. Anxiety disorders develop in around 43 percent of cases. The most common are panic disorder , generalized anxiety disorder , and social anxiety disorder . Anxiety is known to cause deterioration in

1350-526: The initial motor symptoms. Individual presentation of symptoms vary, although most of people affected by PD show an altered circadian rhythm at some point of disease progression. PD is associated with a variety of skin disorders that include melanoma , seborrheic dermatitis , bullous pemphigoid , and rosacea . Seborrheic dermatitis is recognized as a premotor feature that indicates dysautonomia and demonstrates that PD can be detected not only by changes of nervous tissue , but tissue abnormalities outside

1395-400: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=PC12&oldid=906175420 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages PC12 cell line This cell line

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1440-532: The monoamine (dopamine and norepinephrine) pathway, PC12 cells have been reported to express both the kynurenine and serotonin pathways. Support for this assertion includes both RT-PCR evidence for expression of the required enzymes and changes in expression upon treatment with melatonin. A contrary view regarding expression of the serotonin pathway by PC12 cells was expressed by the investigators who first established this cell line. Parkinson%27s disease Parkinson's disease ( PD ), or simply Parkinson's ,

1485-465: The most common NPS and occurs in nearly half of all patients. It features low mood and lack of pleasure and is more prevalent in women. The diagnosis can be challenging since some symptoms of depression such as psychomotor retardation , memory problems, or altered appetite, share similarities with psychiatric signs caused by PD. It may result in suicidal ideation which is more prevalent in PD. Nonetheless, suicidal attempts themselves are lower than in

1530-679: The motor cortex. The hyperdirect pathway is an additional glutamatergic pathway that projects from the frontal lobe to subthalamic nucleus, modulating basal ganglia activity with rapid excitatory input. The striatum and other basal ganglia structures contain D1 and D2 receptor neurons that modulate the previously described pathways. Consequently, dopaminergic dysfunction in these systems can disrupt their respective components— motor , oculomotor , associative , limbic , and orbitofrontal circuits (each named for its primary projection area)—leading to symptoms related to movement, attention, and learning in

1575-528: The nervous system as well. As of 2024, the underlying cause of PD is unknown, yet is assumed to be influenced primarily by an interaction of genetic and environmental factors. Nonetheless, the most significant risk factor is age with a prevalence of 1 percent in those aged over 65 and approximately 4.3 percent in age over 85. Genetic components comprise SNCA , LRRK2 , and PARK2 among others, while environmental risks include exposure to pesticides or heavy metals . Timing of exposure factor may influence

1620-434: The onset of PD. Risk is increased by co-exposure to, for example, glyphosate and MPTP . Harmful heavy metals include mainly manganese , iron , lead , mercury , aluminium , and cadmium . On the other hand, magnesium shows neuroprotective features. Other chemical compounds include trichloroethylene and MPTP . Traumatic brain injury is also strongly implicated as a risk factor. Additionally, although

1665-490: The potential for pharmaceutical alternation of dopamine metabolites such as DOPAL , an autotoxin implicated in the pathology of Parkinson's disease . The PC12 cell line has been used to get more information about diseases of the brain. It has been used in research of hypoxia , where acute hypoxia induces exocytosis and prolonged hypoxia can induce excessive exocytosis. PC12 cells were used to find which prion protein fragments caused neuronal dysfunction. In addition to

1710-437: The progression or severity of certain stages. However, caffeine and nicotine exhibit neuroprotective features, hence lowering the risk of PD. About 85 percent of cases occur sporadic , meaning that there is no family history. PD, in a narrow sense, can be seen as a genetic disease; heritability is estimated to lie between 22 and 40 percent, across different ethnicities. Around 15 percent of diagnosed individuals have

1755-400: The risk for admission to a nursing home . Some of them, such as depression and anxiety, are known to precede characteristic motor signs by up to several years and may herald the development of PD, while most of them worsen as the disease progresses. Research indicates that patients with more severe motor symptoms are at higher risk for any NPS. Conversely, NPS can worsen PD. Depression is

1800-767: The substantia nigra initially presents as movement abnormalities, leading to Parkinson's further categorization as a movement disorder . In 30% of cases, disease progression leads to the cognitive decline known as Parkinson's disease dementia (PDD). Alongside dementia with Lewy bodies , PDD is one of the two subtypes of Lewy body dementia . The four cardinal motor symptoms of Parkinson's— bradykinesia (slowed movements), postural instability , rigidity , and tremor —are called parkinsonism . These four symptoms are not exclusive to Parkinson's and can occur in many other conditions, including HIV infection and recreational drug use . Neurodegenerative diseases that feature parkinsonism but have distinct differences are grouped under

1845-495: The symptoms of PD. Parkinson's disease psychosis (PDP) is present in around 20 percent of cases and comprises hallucinations , illusions and delusions . It is associated with dopaminergic drugs used to treat the motor symptoms, higher morbidity, mortality, a decrease in health-promoting behaviors, and longer nursing home stays. Additionally, it correlates with depression and may herald onset of dementia in advanced stages. Unlike other psychotic forms, PDP typically presents with

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1890-453: The umbrella of Parkinson-plus syndromes or, alternatively, atypical parkinsonian disorders. Parkinson's disease can result from genetic factors or be idiopathic , in which there is no clearly identifiable cause. The latter, also called sporadic Parkinson's, makes up some 85–90% of cases. The defining symptoms affect the motor system and include tremor , bradykinesia , rigidity , and postural instability . Other symptoms may affect

1935-509: The underlying cause is unknown, melanoma is documented to be associated with PD. Low levels of urate in the blood are associated with an increased risk while Helicobacter pylori infection can prevent the absorption of some drugs, including L-DOPA . Main pathological feature is cell death of dopamine -releasing neurons within, among other regions, the basal ganglia , more precisely pars compacta of substantia nigra and partially striatum , thus impeding nigrostriatal pathway of

1980-710: The use of dopamine agonists. Cognitive disturbances can occur in early stages or before diagnosis, and increase in prevalence and severity with duration of the disease. Ranging from mild cognitive impairment to severe Parkinson's disease dementia , they feature executive dysfunction , slowed cognitive processing speed , and disrupted perception and estimation of time. Sleep disorders are common in PD and affect about two thirds of all patients. They comprise insomnia , excessive daytime sleepiness (EDS), restless legs syndrome (RLS), REM sleep behavior disorder (RBD), and sleep-disordered breathing (SDB), many of which can be worsened by medication. RBD may begin years prior to

2025-718: Was first cultured by Greene and Tischler in 1976. It was developed in parallel to the adrenal chromaffin cell model because of its extreme versatility for pharmacological manipulation, ease of culture, and the large amount of information on their proliferation and differentiation. These qualities provide advantage even though they have smaller vesicles and quantal size, holding only an average of 1.9x10 moles of neurotransmitter released. The vesicles hold catecholamines , mostly dopamine , but also limited amount of norepinephrine , and release of these neurotransmitters give rise to spikes due to changes in current similar to chromaffin cells. PC12 cell line use has given much information to

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