Autophagy and Mitochondria: Targets in Neurodegenerative Disorders
Abstract
Background & Objective: Cellular physiology and energy metabolism are maintained by the constant supply of energy furnished by the powerhouses of the cell called mitochondria. Cellular homeostasis depends on the timely clearance of damaged cellular organelles and proteins via pathways including autophagy. Mitochondria and mitochondrial autophagy play a vital role in cellular health and failure of these pathways can have a devastating effect on cellular homeostasis. Amongst the various cell types, neuronal cells are more vulnerable to bioenergetic depletion since most of their functions critically depend on the availability of energy derived from mitochondrial metabolism, thus making neurodegenerative disorders an obstinate issue. Research in the past few decades has shown that these neurodegenerative disorders are associated with mitochondrial dysfunction and compromised mitophagy leading to accumulation of protein aggregates which ultimately culminate in neurodegeneration. Conclusion: Thus, targeting mitochondria and autophagy-related proteins and enzymes in neurodegenerative disorders may open the avenues for potential targets for discovering effective therapies. Here, we review the involvement of mitochondrial and autophagy dysfunction in neurodegenerative disorders specifically focusing on Alzheimer’s, Parkinson’s and Huntington’s disease.
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Mitochondrial failure and impaired autophagy act as amplifiers of proteotoxic stress.
“For example, neuroinflammation is increasingly understood as a central hub that modulates both amyloid and tau pathology [21], while mitochondrial failure and impaired autophagy act as amplifiers of proteotoxic stress [22].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [22]
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Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
- Authors
- Kumar, A., Dhawan, A., Kadam, A., & Shinde, A.
- Affiliations
- National Institute of Pharmaceutical Education and Research (IN)
- Corresponding author
- Kumar, Ashutosh
- ORCID
- Kumar, Ashutosh
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2018-11-02
- Volume
- 17
- Issue
- 9
- Pages
- 696-705
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2886791611
- Cited by
- 49
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 12 · 2019: 7 · 2018: 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- autophagy, mitochondria, mitophagy, neurodegenerative diseases, mitochondrial dysfunction, protein aggregation, Alzheimer's disease, Parkinson's disease, Huntington's disease, bioenergetics, therapeutic target
- MeSH terms
- Animals, Autophagy, Energy Metabolism, Humans, Mitochondria, Neurodegenerative Diseases
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