Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes

Lysosomal Storage Diseases-Regulating Neurodegeneration.

Autophagy is a complex pathway regulated by numerous signaling events that recycles macromolecules and can be perturbed in lysosomal storage diseases (LSDs). The concept of LSDs, which are characterized by aberrant, excessive storage of cellular material in lysosomes, developed following the discovery of an enzyme deficiency as the cause of Pompe disease in 1963. Great strides have since been m...

The neuronal endosomal-lysosomal system in Alzheimer's disease.

Robust activation of the neuronal lysosomal system and cellular pathways converging on the lysosome, such as the endocytic and autophagic pathways, are prominent neuropathological features of Alzheimer's disease. Disturbances of the neuronal endocytic pathway, which are one of the earliest known intracellular changes occurring in Alzheimer's disease and Down syndrome, provide insight into how b...

The Unique Endosomal/Lysosomal System of Giardia lamblia

Lysosomal dysfunction disrupts presynaptic maintenance and restoration of presynaptic function prevents neurodegeneration in lysosomal storage diseases

Lysosomal storage disorders (LSDs) are inherited diseases characterized by lysosomal dysfunction and often showing a neurodegenerative course. There is no cure to treat the central nervous system in LSDs. Moreover, the mechanisms driving neuronal degeneration in these pathological conditions remain largely unknown. By studying mouse models of LSDs, we found that neurodegeneration develops progr...

Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy.

An expansion of polyglutamines in the N terminus of huntingtin causes Huntington's disease (HD) and results in the accrual of mutant protein in the nucleus and cytoplasm of affected neurons. How mutant huntingtin causes neurons to die is unclear, but some recent observations suggest that an autophagic process may occur. We showed previously that huntingtin markedly accumulates in endosomal-lyso...