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The lysosomal system in neuronal cell death: a review
1Laboratories for Molecular Neuroscience, Mailman Research Center, McLean Hospital, Belmont, Massachusetts 02178.
Annals of the New York Academy of Sciences
|May 28, 1993
Summary
Lysosomes are key indicators of neuronal distress in neurodegeneration. Their role, whether in cell death or repair, varies, but they ultimately contribute to cell breakdown and debris removal.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- The lysosomal system is recognized as a significant morphologic marker in distressed or dying neurons.
- Lysosomes and their hydrolases have been implicated in various neuropathologic states, including cell death initiation, repair, and debris scavenging.
- Methodological limitations often hinder a clear distinction between these proposed roles.
Purpose of the Study:
- To explore the multifaceted roles of the lysosomal system in neurodegenerative conditions.
- To investigate the varying degrees of lysosomal involvement in different neurodegenerative states.
- To understand whether lysosomal activation signifies neuronal repair or promotes cell death.
Main Methods:
- Morphologic analysis of neuronal changes in neurodegeneration.
- Investigation of lysosomal system activation and its correlation with other signs of cell injury.
- Examination of intraneuronal storage profiles and residual bodies.
Main Results:
- Lysosomal rupture and hydrolase release are presumed to contribute universally to cell autolysis in late-stage neurodegeneration.
- Lysosomal system involvement varies significantly, with minimal or undetectable activation in some conditions and evident activation alongside cell injury in others.
- Early lysosomal involvement often manifests as intraneuronal accumulation of storage profiles due to primary lysosomal dysfunction or abnormal membrane breakdown.
Conclusions:
- Changes in the lysosomal system are sensitive indicators of neuronal metabolic distress.
- The precise function of lysosomal activation—whether salutary repair or promotion of cell death—remains to be fully elucidated for most neurodegenerative conditions.
- Factors such as species, developmental stage, injury duration, and death pace influence the lysosomal response, with potential differences between vertebrate and invertebrate systems.