Sphingolipids metabolism alteration in the central nervous system: Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases

Alexandra Bouscary; Cyril Quessada; Frédérique René; Michael Spedding; Bradley J Turner; Alexandre Henriques; Shyuan T Ngo; Jean-Philippe Loeffler

doi:10.1016/j.semcdb.2020.10.008

Sphingolipids metabolism alteration in the central nervous system: Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases

Semin Cell Dev Biol. 2021 Apr:112:82-91. doi: 10.1016/j.semcdb.2020.10.008. Epub 2020 Nov 5.

Authors

Alexandra Bouscary¹, Cyril Quessada¹, Frédérique René¹, Michael Spedding², Bradley J Turner³, Alexandre Henriques⁴, Shyuan T Ngo⁵, Jean-Philippe Loeffler⁶

Affiliations

¹ Université de Strasbourg, UMR_S 1118, Fédération de Médecine Translationnelle, CRBS, 1 rue Eugène Boeckel, 67000 Strasbourg, France; INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénérescence, CRBS, 1 rue Eugène Boeckel, 67000 Strasbourg, France.
² Spedding Research Solutions SAS, 6 rue Ampere, 78650 Le Vesinet, France.
³ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia.
⁴ Neuro-sys SAS, 410 chemin Départemental 60, 13120 Gardanne, France.
⁵ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Building 75, Cnr College Rd & Cooper Rd, Brisbane city, QLD 4072, Australia; Centre for Clinical Research, The University of Queensland, Building 71/918, Royal Brisbane & Women's Hospital Campus, Herston, QLD 4029, Australia; Queensland Brain Institute Building 79, The University of Queensland, St Lucia, QLD 4072, Australia.
⁶ Université de Strasbourg, UMR_S 1118, Fédération de Médecine Translationnelle, CRBS, 1 rue Eugène Boeckel, 67000 Strasbourg, France; INSERM, U1118, Mécanismes Centraux et Périphériques de la Neurodégénérescence, CRBS, 1 rue Eugène Boeckel, 67000 Strasbourg, France. Electronic address: [email protected].

PMID: 33160824
DOI: 10.1016/j.semcdb.2020.10.008

Abstract

Sphingolipids are complex lipids. They play a structural role in neurons, but are also involved in regulating cellular communication, and neuronal differentiation and maturation. There is increasing evidence to suggest that dysregulated metabolism of sphingolipids is linked to neurodegenerative processes in amyotrophic lateral sclerosis (ALS), Parkinson's disease and Gaucher's disease. In this review, we provide an overview of the role of sphingolipids in the development and maintenance of the nervous system. We describe the implications of altered metabolism of sphingolipids in the pathophysiology of certain neurodegenerative diseases, with a primary focus on ALS. Finally, we provide an update of potential treatments that could be used to target the metabolism of sphingolipids in neurodegenerative diseases.

Keywords: Ambroxol; Amyotrophic lateral sclerosis; Glucocerebrosidase; Glucosylceramide; Sphingolipids; Therapeutic target.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Amyotrophic Lateral Sclerosis / genetics
Amyotrophic Lateral Sclerosis / metabolism*
Amyotrophic Lateral Sclerosis / pathology
Central Nervous System / metabolism
Central Nervous System / pathology
Humans
Lipid Metabolism / genetics*
Neurodegenerative Diseases / genetics
Neurodegenerative Diseases / metabolism*
Neurodegenerative Diseases / pathology
Sphingolipids / genetics
Sphingolipids / metabolism*

Substances

Sphingolipids