Parkinson’s disease is a common progressive bradykinetic disorder (reduced or slow movement), characterized by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (abnormal deposits of alpha-synuclein). One of its main features is the severe loss of pars-compacta nigral-cell, and the accumulation of α-synuclein aggregations in the brain stem, spinal cord, and cortical regions. Like other neurodegenerative diseases, aging is the major risk factor. This disease commonly causes symptoms like the impairment of motor areas, difficulty in walking, shaking, or, less commonly, a slight dragging of one foot.
The primary pathogenesis of Parkinson’s disease appears to be the accumulation of α-synuclein in various parts of the brain, primarily the substantia nigra, leading to degeneration and subsequent loss of dopamine in the basal ganglia that control muscle tone and movement. An abnormal, post-translationally modified, and aggregated form of the presynaptic protein α-synuclein is the main component of Lewy bodies.
α-synuclein antibodies, which stain Lewy bodies and Lewy neuritis, have become the standard and most sensitive immunohistochemical method for diagnostic purposes. α-synuclein-positive, ubiquitin-negative punctate cytoplasmic staining can also be seen in pigmented brain stem neurons without Lewy bodies and in glial tissue; it represents the earliest stage of abnormal α-synuclein accumulation.
Mutations in the mitochondrial localized PTEN-induced putative kinase 1 (PINK1) have been proven to cause autosomal recessive Parkinson’s disease 6 (PARK6). PINK1 mutations lead to a build-up of improperly folded proteins and the inability to protect neurons from cellular stress and apoptosis. A point mutation in Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) has been seen to cause the autosomal dominant Parkinson’s disease 5 (PARK5). Additionally, a polymorphism in UCHL1, which increases antioxidant activity, may protect against early-onset Parkinson’s Disease.
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