Alpha-synuclein, lipids and Parkinson's disease

Abstract

Parkinson's disease is the second most common neurodegenerative disease, after Alzheimer's disease, among the aging human population. The main symptoms of Parkinson's disease such as tremor and movement disabilities are the result of degeneration of dopaminergic neurons in substantia nigra pars compacta. The widely-accepted subcellular factor which underlies Parkinson's disease neuropathology is the presence of Lewy bodies with characteristic inclusions of aggregated alpha-synuclein. This small soluble protein has been implicated in a range of interactions with phospholipid membranes and free fatty acids. The precise biological function of this protein is, however, still under investigation. Here we review the evidence linking alpha-synuclein, lipid metabolism, fatty acid oxidation, mitochondrial damage and Parkinson's disease. We propose that association of alpha-synuclein with oxidized lipid metabolites can lead to mitochondrial dysfunction in turn leading to dopaminergic neuron death and thus to Parkinson's disease.