Abstract
Lipid and cholesterol metabolism might play a role in the pathogenesis of Parkinson disease (PD). However, the association between cholesterol and PD is not clearly established. Cholesterol accumulation is closely related to the expression of multilamellar bodies (MLBs). Also, cholesterol controls autophagosome transport. Thus, impaired cholesterol and autophagosome trafficking might lead to robust autophagic vacuole accumulation. Our recent work provides the first evidence that the presence of the N370S GBA mutation produces an accumulation of cholesterol, which alters autophagy-lysosome function with the appearance of MLBs, rendering the cell more vulnerable and sensitive to apoptosis.
Keywords:
GBA1; Gaucher disease; Parkinson disease; autophagosomes; cholesterol; lipid storage diseases; lysosomes; multilamellar bodies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autophagosomes / metabolism
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Autophagy / genetics*
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Cholesterol / metabolism
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Glucosylceramidase / metabolism
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Humans
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Lipid Metabolism / genetics
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Lysosomes / genetics
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Lysosomes / metabolism*
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Mutation / genetics*
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Parkinson Disease / genetics*
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Parkinson Disease / pathology
Substances
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Cholesterol
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Glucosylceramidase
Grants and funding
This work was supported by Grants from the Spanish Ministeries of Economía y Competitividad (Secretarıa de Estado de Investigación, Desarrollo e Innovación), Sanidad Política Social e Igualdad and ISCIII, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED): SAF2016-78207-R, PCIN2015-098, CB06/05/0055 and PI2015-2/02 to RM; SAF2013-4759R and CB06/05/0065 to CV; Ramón Areces Fundation (172275) to RM and CV; CB06/05/004 and PI15/00034 and Junta de Extremadura (Consejería de Educación y Empleo):GR15045 to JMF.