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Cells
Volume 14
Issue 12
10.3390/cells14120911
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Review

Autophagy and Alzheimer’s Disease: Mechanisms and Impact Beyond the Brain

by
Zaw Myo Hein
1,
Thirupathirao Vishnumukkala
2,
Barani Karikalan
3,
Aisyah Alkatiri
2,
Farida Hussan
2,
Saravanan Jagadeesan
4,
Mohd Amir Kamaruzzaman
5,
Muhammad Danial Che Ramli
6,
Che Mohd Nasril Che Mohd Nassir
7,* and
Prarthana Kalerammana Gopalakrishna
8,*
1
Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. BOX 346, United Arab Emirates
2
Anatomy Discipline, Human Biology Department, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
3
Department of Pathology, Faculty of Medicine, MAHSA University, Bandar Saujana Putra, Petaling Jaya 42610, Selangor, Malaysia
4
Department of Anatomy, School of Medicine, Taylor’s University, Lakeside Campus, Subang Jaya 47500, Selangor, Malaysia
5
Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
6
Faculty of Health and Life Sciences, Management and Science University, Seksyen 13, Shah Alam 40100, Selangor, Malaysia
7
Department of Anatomy and Physiology, Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu 20400, Terengganu, Malaysia
8
Physiology Discipline, Human Biology Department, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia
*
Authors to whom correspondence should be addressed.
Cells 2025, 14(12), 911; https://doi.org/10.3390/cells14120911 (registering DOI)
Submission received: 26 May 2025 / Revised: 11 June 2025 / Accepted: 12 June 2025 / Published: 16 June 2025
(This article belongs to the Special Issue Biological Mechanisms in the Treatment of Neuropsychiatric Diseases)
Versions Notes

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by neuronal loss, cognitive decline, and pathological hallmarks such as amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Recent evidence highlights autophagy as a pivotal mechanism in cellular homeostasis, mediating the clearance of misfolded proteins and damaged organelles. However, impaired autophagy contributes significantly to AD pathogenesis by disrupting proteostasis, exacerbating neuroinflammation, and promoting synaptic dysfunction. This review aims to scrutinize the intricate relationship between autophagy dysfunction and AD progression, explaining key pathways including macroautophagy, chaperone-mediated autophagy (CMA), and selective autophagy processes such as mitophagy and aggrephagy. This further extends the discussion beyond the central nervous system, evaluating the role of hepatic autophagy in Aβ clearance and systemic metabolic regulation. An understanding of autophagy’s involvement in AD pathology via various mechanisms could give rise to a novel therapeutic strategy targeting autophagic modulation to mitigate disease progression in the future.
Keywords: Alzheimer’s disease; autophagy; amyloid-beta clearance; tau pathology; neurodegeneration Alzheimer’s disease; autophagy; amyloid-beta clearance; tau pathology; neurodegeneration

Share and Cite

MDPI and ACS Style

Hein, Z.M.; Vishnumukkala, T.; Karikalan, B.; Alkatiri, A.; Hussan, F.; Jagadeesan, S.; Kamaruzzaman, M.A.; Ramli, M.D.C.; Che Mohd Nassir, C.M.N.; Gopalakrishna, P.K. Autophagy and Alzheimer’s Disease: Mechanisms and Impact Beyond the Brain. Cells 2025, 14, 911. https://doi.org/10.3390/cells14120911

AMA Style

Hein ZM, Vishnumukkala T, Karikalan B, Alkatiri A, Hussan F, Jagadeesan S, Kamaruzzaman MA, Ramli MDC, Che Mohd Nassir CMN, Gopalakrishna PK. Autophagy and Alzheimer’s Disease: Mechanisms and Impact Beyond the Brain. Cells. 2025; 14(12):911. https://doi.org/10.3390/cells14120911

Chicago/Turabian Style

Hein, Zaw Myo, Thirupathirao Vishnumukkala, Barani Karikalan, Aisyah Alkatiri, Farida Hussan, Saravanan Jagadeesan, Mohd Amir Kamaruzzaman, Muhammad Danial Che Ramli, Che Mohd Nasril Che Mohd Nassir, and Prarthana Kalerammana Gopalakrishna. 2025. "Autophagy and Alzheimer’s Disease: Mechanisms and Impact Beyond the Brain" Cells 14, no. 12: 911. https://doi.org/10.3390/cells14120911

APA Style

Hein, Z. M., Vishnumukkala, T., Karikalan, B., Alkatiri, A., Hussan, F., Jagadeesan, S., Kamaruzzaman, M. A., Ramli, M. D. C., Che Mohd Nassir, C. M. N., & Gopalakrishna, P. K. (2025). Autophagy and Alzheimer’s Disease: Mechanisms and Impact Beyond the Brain. Cells, 14(12), 911. https://doi.org/10.3390/cells14120911

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