Addressing neurodegeneration in lysosomal storage disorders: Advances in Niemann Pick diseases
| Autor: | Ana Toledano-Zaragoza, Maria Dolores Ledesma |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lysosomal Storage Diseases Nervous System Lysosomal storage disorders Early death Mitochondrion medicine.disease_cause Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine medicine Animals Humans Cellular compartment Niemann-Pick Diseases Pharmacology business.industry Neurodegeneration Neurodegenerative Diseases medicine.disease 030104 developmental biology Niemann–Pick disease business Neuroscience 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Neuropharmacology. 171:107851 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2019.107851 |
| Popis: | Most lysosomal storage disorders (LSDs) cause progressive neurodegeneration leading to early death. While the genetic defects that cause these disorders impact all cells of the body, neurons are particularly affected. This vulnerability may be explained by neuronal cells' critical dependence on the lysosomal degradative capacity, as they cannot use division to eliminate their waste. However, mounting evidence supports the extension of storage beyond lysosomes to other cellular compartments (mitochondria, plasma membrane and synapses) as a key event in pathogenesis. Impaired energy supply, oxidative stress, calcium imbalance, synaptic failure and glial alterations may all contribute to neuronal death and thus could be suitable therapeutic targets for these disorders. Here we review the pathological mechanisms underlying neurodegeneration in Niemann Pick diseases and therapeutic strategies developed in animal models and patients suffering from these devastating disorders. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'. |
| Databáze: | OpenAIRE |
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