Altered Bioenergetics and Metabolic Homeostasis in Amyotrophic Lateral Sclerosis.
Neurotherapeutics
; 19(4): 1102-1118, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35773551
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily affects motor neurons and causes muscle atrophy, paralysis, and death. While a great deal of progress has been made in deciphering the underlying pathogenic mechanisms, no effective treatments for the disease are currently available. This is mainly due to the high degree of complexity and heterogeneity that characterizes the disease. Over the last few decades of research, alterations to bioenergetic and metabolic homeostasis have emerged as a common denominator across many different forms of ALS. These alterations are found at the cellular level (e.g., mitochondrial dysfunction and impaired expression of monocarboxylate transporters) and at the systemic level (e.g., low BMI and hypermetabolism) and tend to be associated with survival or disease outcomes in patients. Furthermore, an increasing amount of preclinical evidence and some promising clinical evidence suggests that targeting energy metabolism could be an effective therapeutic strategy. This review examines the evidence both for and against these ALS-associated metabolic alterations and highlights potential avenues for therapeutic intervention.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Neurodegenerativas
/
Esclerose Lateral Amiotrófica
Limite:
Humans
Idioma:
En
Revista:
Neurotherapeutics
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos