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Updated: Jun 17, 2026

Histological Examination of Mitochondrial Morphology in a Parkinson's Disease Model
Published on: June 23, 2023
Dysfunctional mitochondria uphold calpain activation: contribution to Parkinson's disease pathology
A Raquel Esteves1, Daniela M Arduíno, Russell H Swerdlow
1Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-Coimbra, Portugal.
Abstract:
Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, mitochondrial-mediated-calcium homeostasis alterations may lead to its pathologic activation that jeopardizes neuronal structure and function. Here, we provide evidence to support a role for the involvement of calpain 1 in mitochondrial-induced neurodegeneration in a Parkinson's disease (PD) cellular model. We show that dysfunctional mitochondria increases cytosolic calcium, thereby, inducing calpain activation. Interestingly, its inhibition significantly attenuated the accumulation of alpha-synuclein oligomers and contributed to an increase of insoluble alpha-synuclein aggregates, known to be cytoprotective. Moreover, our data corroborate that calpain-1 overactivation in our mitochondrial-deficient cells promote caspase-3 activation. Overall, our findings further clarify the crucial role of dysfunctional mitochondria in the control of molecular mechanisms occurring in PD brain cells, providing a potentially novel correlation between the degradation of calpain substrates suggesting a putative role of calpain and calpain inhibition as a therapeutic tool in PD.
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