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Medicine Notes Neuroscience Notes

Alpha Synuclein And Dopamine In Pd Notes

Updated Alpha Synuclein And Dopamine In Pd Notes

Neuroscience Notes

Neuroscience

Approximately 96 pages

In depth notes covering Neuroscience FHS topics from start to finish. Include suitable references, details on relevant experiments and future areas of research.

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a-Synuclein and dopamine in Parkinson's Disease * * * Cardinal motor symptoms are linked to death of dopaminergic neurons in the nigrostriatal pathway This review asks why these neurons are preferentially susceptible to neurodegeneration in PD and how a-synuclein is involved Brings together recent findings from GWASs - reveal involvement of a-syn gene variants in sporadic PD, with recent studies highlighting important role for a-syn in synaptic transmission and dopaminergic neuron physiology Introduction * * * * * * Cardinal clinical features of PD (rigidity, resting tremor, bradykinesia) - only when 50% of dopaminergic neurons projecting from SNc to striatum are lost Neuropathological hallmark of PD is the presence in surviving SNc neurons of Lewy bodies - composed mainly of a-syn LBs also found in cortex, amygdala, locus coeruleus and peripheral autonomic system o Dysfunction of these extranigral neuronal populations and the presence of LBs correlate with the non-motor manifestations of PD, including autonomic, sleep and olfactory dysfunctions - these can precede motor symptoms PD is an example of a disorder in which a complex mix of aging, genetic susceptibility and environmental insult converge to varying degrees along a spectrum to cause neurodegeneration and disease o It is likely that the majority of sporadic PD cases result from a complex interaction between genes and environment, played out against the background of age, which remains the greatest risk factor A multiple-hit hypothesis has recently been proposed for dopaminergic neuron loss in PD, suggesting the preferential neuronal death results from a combination of toxic cellular insults, from mitochondrial dysfunction or dopamine oxidation, and an impaired stress-induced protective response Effects of a-syn on dopamine homeostasis in presynaptic terminal: o a-syn has been shown to regulate the activity of the enzymes making dopamine (inc. TH) o a-syn might also regulate dopamine vesicle function, including formation by vesicular monoamine transporter 2 (VMAT2) and release into the synaptic cleft o a-syn is necessary for the trafficking of dopamine transporter DAT to the cell surface of the post-synaptic membrane The a-synuclein gene plays a role in both familial and sporadic PD * * a-synuclein gene = SNCA first genetic evidence for the involvement of SNCA in PD was the identification of 3 missense mutations (A30P, E46K, A53T) which segregated with the disease in unrelated families and caused PD with high penetrance

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