The central role of mitochondria in axonal degeneration in multiple sclerosis.
Mult Scler
; 20(14): 1806-13, 2014 Dec.
Article
en En
| MEDLINE
| ID: mdl-25122475
ABSTRACT
Neurodegeneration in multiple sclerosis (MS) is related to inflammation and demyelination. In acute MS lesions and experimental autoimmune encephalomyelitis focal immune attacks damage axons by injuring axonal mitochondria. In progressive MS, however, axonal damage occurs in chronically demyelinated regions, myelinated regions and also at the active edge of slowly expanding chronic lesions. How axonal energy failure occurs in progressive MS is incompletely understood. Recent studies show that oligodendrocytes supply lactate to myelinated axons as a metabolic substrate for mitochondria to generate ATP, a process which will be altered upon demyelination. In addition, a number of studies have identified mitochondrial abnormalities within neuronal cell bodies in progressive MS, leading to a deficiency of mitochondrial respiratory chain complexes or enzymes. Here, we summarise the mitochondrial abnormalities evident within neurons and discuss how these grey matter mitochondrial abnormalities may increase the vulnerability of axons to degeneration in progressive MS. Although neuronal mitochondrial abnormalities will culminate in axonal degeneration, understanding the different contributions of mitochondria to the degeneration of myelinated and demyelinated axons is an important step towards identifying potential therapeutic targets for progressive MS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Axones
/
Esclerosis Múltiple Crónica Progresiva
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Mult Scler
Asunto de la revista:
NEUROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido