Endosomal-lysosomal dysfunction in metabolic diseases and Alzheimer's disease.
Int Rev Neurobiol
; 154: 303-324, 2020.
Article
in En
| MEDLINE
| ID: mdl-32739009
ABSTRACT
The endosomal-lysosomal pathways and related autophagic processes are responsible for proteostasis, involving complexes between lysosomes and autophagosomes. Lysosomes are a key component of homeostasis, involved in cell signaling, metabolism, and quality control, and they experience functional compromise in metabolic diseases, aging, and neurodegenerative diseases. Many genetic mutations and risk factor genes associated with proteinopathies, as well as with metabolic diseases like diabetes, negatively influence endocytic trafficking and autophagic clearance. In contrast, health-improving exercise induces autophagy-lysosomal degradation, perhaps promoting efficient digestion of injured organelles so that undamaged organelles ensure cellular healthiness. Reductions in lysosomal hydrolases are implicated in Alzheimer's, Parkinson's, and lysosomal storage diseases, as well as obesity-related pathology, and members of the cathepsin enzyme family are involved in clearing both Aß42 and α-synuclein. Upregulation of cathepsin hydrolases improves synaptic and memory functions in models of dementia and in exercising humans, thus identifying lysosomal-related systems as vital for healthy cognitive aging.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Exercise
/
Diabetes Mellitus
/
Metabolic Networks and Pathways
/
Alzheimer Disease
/
Proteostasis
/
Synucleinopathies
/
Lysosomes
/
Metabolic Diseases
/
Obesity
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Int Rev Neurobiol
Year:
2020
Document type:
Article
Affiliation country:
United States