Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent; the clinical manifestations of this neurodegenerative disorder include resting tremor, muscular rigidity, bradykinesia, and postural instability. A relatively specific pathological feature accompanying the neuronal degeneration is an intracytoplasmic inclusion body, known as the Lewy body. A mutation was identified in the alpha synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, this mutation may cause a conformational change that renders alpha-synuclein more prone to self aggregation and deposition in Lewy bodies, which finally leads to oxidative stress and misfolding of alpha-synuclein.

Parkin gene, mutations in this gene are reported in early autosomal-recessive form of PD, however these mutations do not degenerate Lewy bodies. The Parkin gene product (Parkin) is involved in protein degradation as a ubiquitin protein ligase, the known substrates of Parkin include PAEL-R (Parkin-associated endothelin receptor-like receptor), Ubiquitination of Pael-R by Parkin leads to its degradation in the proteasome, however failure to ubiquitinate it leads to death of neuron.

Parkin is a 465aa protein in human (chr 6q25.2-q27) and mouse, expressed in many tissues, including brain, heart, testis, and skeletal muscle. In the brain, Parkin is expressed in various regions including substantia nigra.

Alzheimer's Disease (AD) is another neurodegenerative disorder characterized by progressive loss of memory and cognition in the elderly, One of the most important and initial step involves proteolytic cleavage of amyloid precursor protein releasing short 40, 42 & 43 aa peptides, the deposits of these short peptides has been found to contain anti-chymotrypsin (ACT), Apolipoprotein (Apo-E) and two additional proteins named alpha-synuclein and beta-synuclein.

The synuclein exists in 3 isoform alpha-syn (chrm 4q21), a 140aa protein, implicated in pathogenesis of PD and related neurodegenerative disorders, it is mainly expressed in brain specifically in neuronal cell bodies and synapses. The 134 aa beta-syn (chrm 5q35) is homologous to 14 kDa bovine phosphoneuroprotein 14; SCNB has shown to be highly expressed in the substantia nigra of the brain. Recently a new isoform termed gamma-synuclein (SNCG) or breast cancer gene 1 (BCG1) has been cloned (human 127 aa (chrm 10q23), rat/mouse 123 aa). Higher levels of expression of SNCG have been reported in advanced breast carcinomas. All three synuclein show ~40% identity.

Publications on Parkin and Synuclein-alpha using ADI's Antibodies:

Parkin, Hase A et al 2002 Brain Res. 930, 143-149 Characterization of parkin in bovine peripheral nerve.
 

Synuclein-alpha, Sudo S et al 2002 Acta Neuropathologica DOI 10.1007 Motor neuron disease with dementia combined with degeneration of striatonigral and pallidoluysian systems.