SNCA A30P/A53T Human
Description
Product Specs
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAP GKTKEGVLYV GSKTKEGVVH GVTTVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKNEEGAPQE GILEDMPVDP DNEAYEMPSE EGYQDYEPEA.
Product Science Overview
Alpha-synuclein (α-synuclein) is a protein that plays a crucial role in the pathogenesis of several neurodegenerative diseases, collectively known as synucleinopathies. These include Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). The protein is predominantly expressed in the brain, particularly in the presynaptic terminals of neurons, where it is involved in synaptic vesicle regulation and neurotransmitter release .
Mutations in the α-synuclein gene (SNCA) are linked to familial forms of Parkinson’s disease. Among these, the A30P and A53T mutations are particularly noteworthy. These mutations result in the substitution of alanine with proline at position 30 (A30P) and alanine with threonine at position 53 (A53T) of the α-synuclein protein .
- A30P Mutation: This mutation is associated with a similar age of onset and symptoms as sporadic PD. However, it leads to a reduced speed of movement and an increased paralysis rate in model organisms .
- A53T Mutation: This mutation generally results in an earlier age of onset and accelerated progression of the disease. It significantly decreases both the speed and frequency of body movements and increases the paralysis rate .
The aggregation of α-synuclein is a hallmark of Parkinson’s disease and other synucleinopathies. The A30P and A53T mutations enhance the propensity of α-synuclein to form aggregates, which are toxic to neurons. These aggregates, known as Lewy bodies, disrupt normal cellular functions and lead to neuronal death .
Various model organisms, including transgenic mice and C. elegans, have been used to study the effects of these mutations. For instance, transgenic mice overexpressing human wild-type, A30P, or A53T α-synuclein have shown a high correlation with the toxic gain of function mechanism for α-synuclein pathogenesis . In C. elegans models, the expression of these mutational variants in muscle cells has provided insights into their behavioral and pathological impacts .
Understanding the molecular mechanisms underlying α-synuclein aggregation and toxicity is crucial for developing therapeutic strategies. Research is ongoing to identify compounds that can inhibit α-synuclein aggregation or promote its clearance from neurons. Additionally, gene therapy approaches are being explored to correct or mitigate the effects of these mutations .
