Lipids in the Physiopathology of Hereditary Spastic Paraplegias.

Frédéric Darios, Fanny Mochel, Giovanni Stevanin
Front. Neurosci.. 2020-02-28; 14:
DOI: 10.3389/fnins.2020.00074

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1. Front Neurosci. 2020 Feb 28;14:74. doi: 10.3389/fnins.2020.00074. eCollection
2020.

Lipids in the Physiopathology of Hereditary Spastic Paraplegias.

Darios F(1)(2)(3)(4), Mochel F(1)(2)(3)(4)(5), Stevanin G(1)(2)(3)(4)(6).

Author information:
(1)Sorbonne Université, Paris, France.
(2)Inserm, U1127, Paris, France.
(3)CNRS, UMR 7225, Paris, France.
(4)Institut du Cerveau et de la Moelle Epinière, Paris, France.
(5)National Reference Center for Neurometabolic Diseases, Pitié-Salpêtrière
University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
(6)Equipe de Neurogénétique, Ecole Pratique des Hautes Etudes, PSL Research
University, Paris, France.

Hereditary spastic paraplegias (HSP) are a group of neurodegenerative diseases
sharing spasticity in lower limbs as common symptom. There is a large clinical
variability in the presentation of patients, partly underlined by the large
genetic heterogeneity, with more than 60 genes responsible for HSP. Despite this
large heterogeneity, the proteins with known function are supposed to be involved
in a limited number of cellular compartments such as shaping of the endoplasmic
reticulum or endolysosomal function. Yet, it is difficult to understand why
alteration of such different cellular compartments can lead to degeneration of
the axons of cortical motor neurons. A common feature that has emerged over the
last decade is the alteration of lipid metabolism in this group of pathologies.
This was first revealed by the identification of mutations in genes encoding
proteins that have or are supposed to have enzymatic activities on lipid
substrates. However, it also appears that mutations in genes affecting
endoplasmic reticulum, mitochondria, or endolysosome function can lead to changes
in lipid distribution or metabolism. The aim of this review is to discuss the
role of lipid metabolism alterations in the physiopathology of HSP, to evaluate
how such alterations contribute to neurodegenerative phenotypes, and to
understand how this knowledge can help develop therapeutic strategy for HSP.

Copyright © 2020 Darios, Mochel and Stevanin.

DOI: 10.3389/fnins.2020.00074
PMCID: PMC7059351
PMID: 32180696

Auteurs Bordeaux Neurocampus