About this Research Topic

Background

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with a current life time risk of 2% for men and 1.3% for women, which is predicted to increase in the next decades. PD is characterized by both motor and non-motor symptoms, known to be linked to progressive loss of dopaminergic neurons in the substantia nigra projecting to the striatum, formation of Lewy bodies and activation of microglia. This knowledge has been mainly obtained from studies based on the familial forms of PD, which only account for around 10% of the cases, and toxins that mimic some of the PD pathological hallmarks. However, these studies did not fully elucidate the molecular mechanisms underlying PD or lead to the development of disease-modifying treatments. Most of the research on PD performed up to now has been focused on the contribution of a number of (familial) genes and proteins to the disease, but recent evidence indicates that lipids might play a crucial role in the pathogenesis of this devastating neurodegenerative disease.

Lipids are a heterogeneous family of biomolecules grouped together not by the presence of specific structural characteristics, but by their solubility in nonpolar organic solvents. Lipids are mainly known by their role in energy storage, but they are also crucial components of lipid membranes and lipid rafts, intracellular signaling pathways and immune system modulation. Mutations or single-nucleotide polymorphisms (SNPs) in genes encoding enzymes and transcription factors involved in lipid metabolism, such as GBA, SMPD1 or SREBF1, have been recently found to be associated with PD. Moreover, central processes in PD, such as formation of α-synuclein aggregates (which are one of the main components of Lewy bodies), oxidative stress and immune system activation, have been shown to be modulated by lipid composition. Additionally, dietary intake of cholesterol and polyunsaturated fatty acids, and treatment with cholesterol-lowering drugs (statins) seem to affect PD risk.

Therefore, the study of the role of lipids in PD, which has not been widely considered until now, might be of great importance to have a better understanding of the disease and to develop effective treatments and dietary interventions that not only improve the quality of life of patients, but that slow down or stop its progression.

Keywords: Parkinson’s disease, lipids, lipoproteins, intracellular signaling, metabolism

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