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The Parkinson Disease gene SNCA: Evolutionary and structural insights with pathological implication
Irum Javaid Siddiqui1, Nashaiman Pervaiz1, Amir Ali Abbasi1
1National Center for Bioinformatics, Program of Comparative and Evolutionary Genomics, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Scientific Reports
|April 16, 2016
Summary
Parkinson's disease (PD) involves alpha synuclein (SNCA). Evolutionary analysis reveals a critical N-terminal region (residues 32-58) in SNCA, vital for protein stability and disease pathogenesis.
Area of Science:
- Neuroscience
- Evolutionary Biology
- Biochemistry
Background:
- Parkinson's disease (PD) is the second leading neurodegenerative disorder after Alzheimer's.
- Alpha synuclein (SNCA) is a key component of Lewy bodies, a hallmark of PD neuropathology.
- Five known mutations in SNCA cause autosomal dominant forms of PD.
Purpose of the Study:
- To investigate the evolutionary and structural characteristics of SNCA.
- To analyze sequence and structural evolution of SNCA within sarcopterygians.
- To compare SNCA with its paralogs, SNCB and SNCG.
Main Methods:
- Comparative sequence analysis across sarcopterygian species.
- Rate analysis to detect evolutionary selection pressures.
- Structural dynamics modeling to understand protein evolution.
Main Results:
- Strong purifying selection was observed across the entire synuclein family.
- A specific region (residues 32-58) in the SNCA N-terminal domain gained functional importance during sarcopterygian evolution.
- This critical region's significance is attributed to lineage-specific substitutions and epistatic interactions.
Conclusions:
- The N-terminal region (residues 32-58) of SNCA is evolutionarily critical.
- This region is essential for protein stability, proper conformation, and disease pathogenesis.
- The identified region harbors key interaction sites relevant to PD.
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