Mesenchymal stem cells for lysosomal storage and polyglutamine disorders: Possible shared mechanisms.

Abstract

Mesenchymal stem cells' (MSC) therapeutic potential has been investigated for the treatment of several neurodegenerative diseases. The fact these cells can mediate a beneficial effect in different neurodegenerative contexts strengthens their competence to target diverse mechanisms. On the other hand, distinct disorders may share similar mechanisms despite having singular neuropathological characteristics. We have previously shown that MSC can be beneficial for two disorders, one belonging to the groups of Lysosomal Storage Disorders (LSDs) - the Krabbe Disease or Globoid Cell Leukodystrophy, and the other to the family of Polyglutamine diseases (PolyQs) - the Machado-Joseph Disease or Spinocerebellar ataxia type 3. We gave also input into disease characterization since neuropathology and MSC's effects are intrinsically associated. This review aims at describing MSC's multimode of action in these disorders while emphasizing to possible mechanistic alterations they must share due to the accumulation of cellular toxic products. Lysosomal storage disorders and PolyQs have different aetiology and associated symptoms, but both result from the accumulation of undegradable products inside neuronal cells due to inefficient clearance by the endosomal/lysosomal pathway. Moreover, numerous cellular mechanisms that become compromised latter are also shared by these two disease groups. Here, we emphasize MSC's effect in improving proteostasis and autophagy cycling turnover, neuronal survival, synaptic activity and axonal transport. LSDs and PolyQs, though rare in their predominance, collectively affect many people and require our utmost dedication and efforts to get successful therapies due to their tremendous impact on patient s' lives and society.