Parkinson’s Disease-Related Genes and Lipid Alteration

International Journal of Molecular Sciences

Manuela Galioto¹  Ciro Iaccarino¹  Milena Fais¹  Claudia Crosio¹  Grazia Galleri²  Antonio Dore³ 

[1] Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy;Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy;Istituto di Scienza delle Produzioni Alimentari, CNR, 07040 Sassari, Italy;

关键词: Parkinson’s disease;    lipid metabolism;    alpha-synuclein;    GBA;    LRRK2;   

DOI  :  10.3390/ijms22147630

来源: DOAJ

【 摘 要 】

Parkinson’s disease (PD) is a complex and progressive neurodegenerative disorder with a prevalence of approximately 0.5–1% among those aged 65–70 years. Although most of its clinical manifestations are due to a loss of dopaminergic neurons, the PD etiology is largely unknown. PD is caused by a combination of genetic and environmental factors, and the exact interplay between genes and the environment is still debated. Several biological processes have been implicated in PD, including mitochondrial or lysosomal dysfunctions, alteration in protein clearance, and neuroinflammation, but a common molecular mechanism connecting the different cellular alterations remains incompletely understood. Accumulating evidence underlines a significant role of lipids in the pathological pathways leading to PD. Beside the well-described lipid alteration in idiopathic PD, this review summarizes the several lipid alterations observed in experimental models expressing PD-related genes and suggests a possible scenario in relationship to the molecular mechanisms of neuronal toxicity. PD could be considered a lipid-induced proteinopathy, where alteration in lipid composition or metabolism could induce protein alteration—for instance, alpha-synuclein accumulation—and finally neuronal death.

【 授权许可】

Unknown