ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease

Riya Thapa; Ehssan Moglad; Muhammad Afzal; Gaurav Gupta; Asif Ahmad Bhat; Waleed Hassan Almalki; Imran Kazmi; Sami I Alzarea; Kumud Pant; Haider Ali; Keshav Raj Paudel; Harish Dureja; Thakur Gurjeet Singh; Sachin Kumar Singh; Kamal Dua

doi:10.1016/j.arr.2024.102327

ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease

Ageing Res Rev. 2024 May 10:98:102327. doi: 10.1016/j.arr.2024.102327. Online ahead of print.

Authors

Riya Thapa¹, Ehssan Moglad², Muhammad Afzal³, Gaurav Gupta⁴, Asif Ahmad Bhat⁵, Waleed Hassan Almalki⁶, Imran Kazmi⁷, Sami I Alzarea⁸, Kumud Pant⁹, Haider Ali¹⁰, Keshav Raj Paudel¹¹, Harish Dureja¹², Thakur Gurjeet Singh¹³, Sachin Kumar Singh¹⁴, Kamal Dua¹⁵

Affiliations

¹ Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
² Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia.
³ Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia.
⁴ Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India. Electronic address: gauravpharma25@gmail.com.
⁵ School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Mahal Road, Jaipur, India.
⁶ Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
⁷ Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia.
⁸ Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Sakaka, Aljouf, Saudi Arabia.
⁹ Graphic Era (Deemed to be University), Clement Town, Dehradun 248002, India; Graphic Era Hill University, Clement Town, Dehradun 248002, India.
¹⁰ Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, India; Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan.
¹¹ Centre of Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW 2007, Australia.
¹² Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India.
¹³ Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India.
¹⁴ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia.
¹⁵ Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.

PMID: 38734148
DOI: 10.1016/j.arr.2024.102327

Abstract

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.

Keywords: Autophagy; Genetic Regulation; LncRNAs; MiRNAs; NcRNAs; Parkinson's disease.

Publication types

Review