The 14-kDa protein α-synuclein is closely associated with Parkinson's disease (PD), dementia with Lewy bodies (DLB), and other synucleinopathies such as multiple system atrophy, and even certain forms of Alzheimer's disease. Deciphering the biochemistry of αS in native systems is key to developing therapeutics.
Deciphering the biochemistry of αS in native systems is key to developing therapeutics. αS is highly expressed in the brain, the second most lipid-rich organ, and has been proposed to be a lipid-binding protein that physiologically interacts with phospholipids and fatty acids (FAs).
Excessive αS membrane interactions may lead to αS protein aggregation by inducing its protonucleation. However, αS may also exert its toxicity before or independently of its self-assembly, for example, via excessive membrane interactions, which can be enhanced by certain lipids and FAs.
There is a complex αS lipid landscape that encompasses physiological and pathological states of αS, with new insights into the formation of Lewy lesions emerging, new drug candidates for lipid-related PD emerging, and genome-wide association studies (GWAS) increasingly validating new findings in lipid-related pathways.
Deciphering the biochemistry of αS in native systems is key to developing therapeutics. αS is highly expressed in the brain, the second most lipid-rich organ, and has been proposed to be a lipid-binding protein that physiologically interacts with phospholipids and fatty acids (FAs).
Excessive αS membrane interactions may lead to αS protein aggregation by inducing its protonucleation. However, αS may also exert its toxicity before or independently of its self-assembly, for example, via excessive membrane interactions, which can be enhanced by certain lipids and FAs.
There is a complex αS lipid landscape that encompasses physiological and pathological states of αS, with new insights into the formation of Lewy lesions emerging, new drug candidates for lipid-related PD emerging, and genome-wide association studies (GWAS) increasingly validating new findings in lipid-related pathways.
