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About SNCA / Synuclein:
Synucleins are soluble proteins found in all vertebrates that are largely expressed in brain tissue and some malignancies.
The term is a combination of the words "synapse" and "nucleus," as discovered in the synapses of the electric ray's electromotor nucleus.
There are three known proteins in the synuclein family: alpha-synuclein, beta-synuclein, and gamma-synuclein. When alpha-synuclein was shown to be mutated in multiple families with autosomal dominant Parkinson's disease, researchers became interested in the synuclein family.
A highly conserved alpha-helical lipid-binding motif shared by all synucleins is similar to the class-A2 lipid-binding domains of exchangeable apolipoproteins. Members of the synuclein family are not found outside of vertebrates, albeit they share some structural similarities with plant 'late-embryo-abundant' proteins.
SNCA Structure
A-synuclein N-terminus has seven 11-residue repeats that are predicted to create an amphipathic alpha-helix. The repetitions are extremely conserved, both across species and among the three isoforms. The motif is also distinct, with no other sequences found outside of the synuclein family. Furthermore, this sequence has only been found in vertebrates, including the lamprey.
Synuclein Function
None of the synuclein proteins have been shown to have normal cellular activities. Some evidence suggests that it plays a role in the regulation of membrane stability and/or turnover. Alpha-synuclein mutations have been linked to early-onset familial Parkinson's disease, and the protein accumulates inappropriately in Parkinson's disease, Alzheimer's disease, Lewy body disease, and other neurodegenerative illnesses. The expression of the gamma-synuclein protein in breast cancers is a marker for tumor progression.