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Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases

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Abstract

It is considered a significant challenge to understand the neuronal cell death mechanisms with a suitable cure for neurodegenerative disorders in the coming years. Calpains are one of the best-considered “cysteine proteases activated” in brain disorders. Calpain is an important marker and mediator in the pathophysiology of neurodegeneration. Calpain activation being the essential neurodegenerative factor causing apoptotic machinery activation, it is crucial to develop reliable and effective approaches to prevent calpain-mediated apoptosis in degenerating neurons. It has been recently seen that the “inhibition of calpain activation” has appeared as a possible therapeutic target for managing neurodegenerative diseases. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was conducted. The present article reviews the basic pathobiology and role of selective calpain inhibitors used in various neurodegenerative diseases as a therapeutic target.

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Abbreviations

NDD:

Neurodegenerative diseases

NFTs:

Neurofibrillary tangles

APP:

Amyloid precursor protein

MAPK:

Mitogen activated protein kinase

CDK5:

Cyclin‐dependent kinase 5

PP2A:

Protein phosphatase 2A

GSK3β:

Glycogen synthase kinase 3β

CII:

Cerebral ischemic injury

TBI:

Traumatic brain injury

ABCA1:

ATP‐binding cassette transporter A1

SOD-1:

Superoxide dismutase 1

ALS:

Amyotrophic lateral sclerosis

PD:

Parkinson’s disease

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

HD:

Huntington’s disease

Htt:

Huntingtin gene

TBI:

Traumatic brain injury

BDPs:

Breakdown products

CMS:

Calpain-mediated spectrin

CSF:

Cerebrospinal fluid

OGD:

Oxygen–glucose deprivation

CaN:

Calcineurin

mSOD:

Superoxide dismutase

ROS:

Reactive oxygen species

TLE:

Temporal lobe epilepsy

SCI:

Spinal cord injury

IC:

Intracellular

CAST:

Calpastatin

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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Author notes

  1. Heena Khan and Nikhil Garg have contributed equally in this study.

Authors and Affiliations

  1. Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India

    Heena Khan, Nikhil Garg, Thakur Gurjeet Singh & Amarjot Kaur

  2. Chitkara School of Pharmacy, Chitkara University, Baddi, Himachal Pradesh, India

    Komal Thapa

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  1. Heena Khan
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Contributions

Conceptualization: Conceived and designed the experiments: TGS. Analyzed the data: HK, KT, NG wrote the manuscript: HK, NG. Editing of the manuscript: AK. Critically reviewed the article: TGS. All authors read and approved the final manuscript.

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Correspondence to Thakur Gurjeet Singh.

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Khan, H., Garg, N., Singh, T.G. et al. Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases. Neurochem Res 47, 1125–1149 (2022). https://doi.org/10.1007/s11064-021-03521-9

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  • DOI: https://doi.org/10.1007/s11064-021-03521-9

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