Calpain in the Cleavage of Alpha-synuclein and the Pathogenesis of Parkinson's Disease

Overview

Journal Prog Mol Biol Transl Sci

Specialty Molecular Biology

Date 2019 Oct 12

PMID 31601400

Citations 10

Authors

Ramsha Shams

Naren L Banik

Azizul Haque

Affiliations

Soon will be listed here.

Abstract

Parkinson's disease (PD) devastates 6.3 million people, ranking it as one of the most prevalent neurodegenerative motor disorders worldwide. PD patients may manifest symptoms of postural instability, bradykinesia, and resting tremors as a result of increasing α-synuclein aggregation and neuron death with disease progression. Therapy options are limited, and those available to patients may worsen their condition. Thus, investigations to understand disease progression may help develop therapeutic strategies for improvement of quality of life for patients suffering from PD. This review provides an overview of α-synuclein, a presynaptic neuronal protein whose function in the healthy brain and PD pathology remains a mystery. This review also focuses on calcium-induced activation of calpain, a neutral protease, and the subsequent cascade of cellular processing of α-synuclein and emerging defense responses observed in experimental models of PD: microglial activation, dysregulation of T cells, and inflammatory responses in the brain. In addition, this review discusses the events of cross presentation of synuclein peptides by professional antigen presenting cells and microglia, induction of inflammatory responses in the periphery and brain, and emerging calpain-targeted therapeutic strategies to attenuate neuronal death in PD.

Citing Articles

Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson's Disease and Aging.

Gathings A, Zaman V, Banik N, Haque A Biomedicines. 2024; 12(5).

PMID: 38791036 PMC: 11117523. DOI: 10.3390/biomedicines12051074.

Membrane-anchored calpains - hidden regulators of growth and development beyond plants?.

Safranek M, Shumbusho A, Johansen W, Sarkanova J, Vosko S, Bokor B Front Plant Sci. 2024; 14:1289785.

PMID: 38173928 PMC: 10762896. DOI: 10.3389/fpls.2023.1289785.

Calpain signaling: from biology to therapeutic opportunities in neurodegenerative disorders.

Metwally E, Al-Abbadi H, Hussain T, Murtaza G, Abdellatif A, Ahmed M Front Vet Sci. 2023; 10:1235163.

PMID: 37732142 PMC: 10507866. DOI: 10.3389/fvets.2023.1235163.

Role and Dysregulation of miRNA in Patients with Parkinson's Disease.

Salemi M, Marchese G, Lanza G, Cosentino F, Salluzzo M, Schillaci F Int J Mol Sci. 2023; 24(1).

PMID: 36614153 PMC: 9820759. DOI: 10.3390/ijms24010712.

Inhibition of Calpain Attenuates Degeneration of Substantia Nigra Neurons in the Rotenone Rat Model of Parkinson's Disease.

Zaman V, Drasites K, Myatich A, Shams R, Shields D, Matzelle D Int J Mol Sci. 2022; 23(22).

PMID: 36430329 PMC: 9694996. DOI: 10.3390/ijms232213849.

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