L-Arginine Ameliorates Defective Autophagy in GM2 Gangliosidoses by mTOR Modulation.

ABSTRACT:

Aims

Tay-Sachs and Sandhoff diseases (GM2 gangliosidosis) are autosomal recessive disorders of lysosomal function that cause progressive neurodegeneration in infants and young children. Impaired hydrolysis catalysed by β-hexosaminidase A (HexA) leads to the accumulation of GM2 ganglioside in neuronal lysosomes. Despite the storage phenotype, the role of autophagy and its regulation by mTOR has yet to be explored in the neuropathogenesis. Accordingly, we investigated the effects on autophagy and lysosomal integrity using skin fibroblasts obtained from patients with Tay-Sachs and Sandhoff diseases.

Results

Pathological autophagosomes with impaired autophagic flux, an abnormality confirmed by electron microscopy and biochemical studies revealing the accelerated release of matur

SUBMITTER: Castejon-Vega B 

PROVIDER: S-EPMC8619250 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature