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Published on: December 19, 2017
Therapeutic Potential of α-Crystallins in Retinal Neurodegenerative Diseases
Ashutosh S Phadte1, Zachary B Sluzala1, Patrice E Fort1,2
1Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Abstract:
The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.
Insights
Alpha-crystallins (alphaA- and alphaB-) show promise in preventing cell death and neurodegeneration. However, their therapeutic potential for chronic neurodegenerative diseases requires further investigation and functional enhancement.
Area of Science:
- Biochemistry
- Neuroscience
- Ophthalmology
Background:
- Alpha-crystallins (alphaA- and alphaB-) are known for chaperone and anti-apoptotic activities.
- Their upregulation in neurodegenerative disease models suggests a protective role against stress.
- However, functional decline of alpha-crystallins in chronic conditions remains a concern.
Purpose of the Study:
- To review the literature on the anti-apoptotic potential of alphaA- and alphaB-crystallins in retinal neurodegenerative diseases.
- To explore strategies for modulating alpha-crystallin function for therapeutic benefit.
- To assess the potential of functionally enhanced alpha-crystallins in promoting neuronal survival.
Main Methods:
- Literature review of studies on alpha-crystallins and neurodegeneration.
- Analysis of research on alpha-crystallin chaperone and anti-apoptotic functions.
- Evaluation of potential therapeutic applications in retinal diseases.
Main Results:
- Alpha-crystallins exhibit significant anti-apoptotic and neuroprotective properties.
- Evidence suggests a role in adaptive responses to neurodegenerative stress.
- Functional impairment of alpha-crystallins can occur in chronic neurodegenerative conditions.
Conclusions:
- Alpha-crystallins hold therapeutic promise for neurodegenerative diseases, particularly retinal conditions.
- Modulating and enhancing their function could improve neuronal viability.
- Further research is needed to clarify their role and optimize their use as protein-based therapeutics.
