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Intracellular DAMPs in Neurodegeneration and Their Role in Clinical Therapeutics

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Abstract

Neuroinflammation is the major implication of neurodegeneration. This is a complex process which initiates from the cellular injury triggering the innate immune system which gives rise to damage-associated molecular patterns (DAMPs) which are also recognized as endogenous danger indicators. These originate from various compartments of the cell under pathological stimulus. These are very popular candidates having their origin in the intracellular compartments and organelles of the cell and may have their site of action itself in the intracellular or at the extracellular spaces. Under the influence of the pathological stimuli, they interact with the pattern-recognition receptor to initiate their pro-inflammatory cascade followed by the cytokine release. This provides a good opportunity for diagnostic and therapeutic interventions creating better conditions for repair and reversal. Since the major contributors arise from the intracellular compartment, in this review, we have attempted to focus on the DAMP molecules arising from the intracellular compartments and their specific roles in the neurodegenerative events explaining their downstream mediators and signaling. Moreover, we have tried to cover the latest interventions in terms of DAMPs as clinical biomarkers which can assist in detecting the disease and also target it to reduce the innate-immune activation response which can help in reducing the sterile neuroinflammation having an integral role in the neurodegenerative processes.

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Data Availability

Data presented in this study have been published by the authors of the cited studies and are openly available.

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Acknowledgements

The authors acknowledge the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Government of India, for their support. NIPER, Raebareli communication number for this manuscript is NIPER-R/Communication/370.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER-R), Lucknow, UP, 226002, India

    Jasleen Kaur & Saba Naqvi

  2. Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Lucknow, UP, 226002, India

    Harsimar Singh & Saba Naqvi

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  1. Jasleen Kaur
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  2. Harsimar Singh
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  3. Saba Naqvi
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Jasleen Kaur. The first draft of the manuscript was written by Jasleen Kaur. Diagram illustrations were done by Harsimar Singh, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Saba Naqvi.

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Kaur, J., Singh, H. & Naqvi, S. Intracellular DAMPs in Neurodegeneration and Their Role in Clinical Therapeutics. Mol Neurobiol 60, 3600–3616 (2023). https://doi.org/10.1007/s12035-023-03289-9

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