More than meets the eye in Parkinson’s disease and other synucleinopathies: from proteinopathy to lipidopathy.

Publication date: Jul 08, 2023

The accumulation of proteinaceous inclusions in the brain is a common feature among neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). The main neuropathological hallmark of PD and DLB are inclusions, known as Lewy bodies (LBs), enriched not only in α-synuclein (aSyn), but also in lipid species, organelles, membranes, and even nucleic acids. Furthermore, several genetic risk factors for PD are mutations in genes involved in lipid metabolism, such as GBA1, VSP35, or PINK1. Thus, it is not surprising that mechanisms that have been implicated in PD, such as inflammation, altered intracellular and vesicular trafficking, mitochondrial dysfunction, and alterations in the protein degradation systems, may be also directly or indirectly connected through lipid homeostasis. In this review, we highlight and discuss the recent evidence that suggests lipid biology as important drivers of PD, and which require renovated attention by neuropathologists. Particularly, we address the implication of lipids in aSyn accumulation and in the spreading of aSyn pathology, in mitochondrial dysfunction, and in ER stress. Together, this suggests we should broaden the view of PD not only as a proteinopathy but also as a lipidopathy.

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Concepts Keywords
Genetic Alpha-synuclein
Homeostasis Lipidopathy
Lipidopathy Lipidostasis
Parkinson Neurodegeneration
Recent Parkinson’s disease


Type Source Name
disease MESH synucleinopathies
disease MESH proteinopathy
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH dementia
disease MESH inflammation
drug DRUGBANK Isoxaflutole
drug DRUGBANK Coenzyme M
disease MESH point mutations
disease MESH death
drug DRUGBANK Dopamine
drug DRUGBANK Serine
drug DRUGBANK Methylergometrine
disease MESH disease progression
drug DRUGBANK Cholesterol
drug DRUGBANK Phosphatidylethanolamine
drug DRUGBANK Coenzyme A
drug DRUGBANK Tretamine
drug DRUGBANK Boron
pathway KEGG Metabolic pathways
disease MESH pathogenesis
drug DRUGBANK Palmitic Acid
drug DRUGBANK Glutamic Acid
drug DRUGBANK Dextrose unspecified form
pathway KEGG Lysosome
pathway KEGG Sphingolipid metabolism
disease MESH haploinsufficiency
disease MESH cognitive impairment
disease MESH defects
drug DRUGBANK Sodium lauryl sulfate
pathway KEGG Autophagy
drug DRUGBANK Hexadecanal
drug DRUGBANK Glycine
drug DRUGBANK Sulfate ion
drug DRUGBANK Phosphate ion
drug DRUGBANK Oleic Acid
pathway KEGG Proteasome
disease MESH shock
disease MESH lysosomal storage diseases
drug DRUGBANK L-Threonine
drug DRUGBANK Trihexyphenidyl
drug DRUGBANK Profenamine
pathway KEGG Mitophagy
drug DRUGBANK Methoxy polyethylene glycol-epoetin beta
drug DRUGBANK Phosphatidyl serine
drug DRUGBANK Cardiolipin
drug DRUGBANK Omega-3 fatty acids
drug DRUGBANK Fructose
drug DRUGBANK Spinosad
disease MESH Lewy body disease
disease MESH primary parkinsonism
pathway KEGG Parkinson disease
drug DRUGBANK Honey
drug DRUGBANK Carboxyamidotriazole
disease MESH immune disorders
drug DRUGBANK Methyl isocyanate
disease MESH Parkinsonism
disease MESH neuroblastoma
drug DRUGBANK Zanamivir
disease MESH Glucocerebrosidase deficiency
drug DRUGBANK Phosphorus
disease MESH metabolic diseases
drug DRUGBANK Alpha-methyltryptamine
disease MESH endoplasmic reticulum stress
disease MESH liver steatosis
disease MESH Sid
drug DRUGBANK L-Lysine
disease MESH starvation
disease MESH neurological disorders
drug DRUGBANK L-Asparagine
pathway KEGG Peroxisome
disease MESH hypertriglyceridemia
drug DRUGBANK Huperzine B

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