Lysosomal storage disorders (LSDs) often involve neurodegeneration due to accumulation of toxic metabolites.
Enzyme deficiencies lead to substrate accumulation in lysosomes, causing neuronal dysfunction and death.
¶ Key Disorders and Affected Neurons
- Cortical neurons: Severe involvement
- Cerebellar Purkinje cells: Ataxia
- Basal ganglia: Movement disorders
- Cortical pyramidal neurons: Early loss
- Motor neurons: Progressive weakness
- Retinal ganglion cells: Cherry-red spot
- Cortical neurons: Dementia
- Purkinje cells: Ataxia
- Hippocampal neurons: Memory loss
- Cortical neurons: Early involvement
- Motor neurons: Progressive weakness
- Oligodendrocytes: Demyelination
- Lipids, glycoproteins, mucopolysaccharides
- Lysosomal distension
- Autophagy blockade
- Lysosomal calcium mishandling
- ER-lysosomal crosstalk
- Membrane trafficking defects
- Limited CNS efficacy
- Emerging BBB-crossing enzymes
- Miglustat, eliglustat
- Reduces substrate production
- AAV-mediated delivery
- Early intervention critical
- Lysosomal storage disorders and neurodegeneration (2022)
- Neuronal pathology in LSDs (2021)