Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease.

Satinder Kaur, Abhishek Sehrawat, Sarabjit Singh Mastana, Ramesh Kandimalla, Pushpender Kumar Sharma, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti

Journal: Life sciences 2023;330():121995

PMID: 37541578

Full Text on Elsevier Science View on PubMed

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory.

Address: Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India.; School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK. Electronic address: [email protected].; CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Telangana, India.; Amity Institute of Biotechnology, Amity University Rajasthan, India. Electronic address: [email protected].; Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India. Electronic address: [email protected].; Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India. Electronic address: [email protected].

DOI: 10.1016/j.lfs.2023.121995

Link outs

Free resources

Medical:

https://medlineplus.gov/parkinsonsdisease.html

Miscellaneous:

https://assays.cancer.gov/CPTAC-71

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0024...

MeSH Terms: Humans, Parkinson Disease, Calcium, Endoplasmic Reticulum, Dopaminergic Neurons, Homeostasis