The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration

Heras-Sandoval, David; Pérez-Rojas, Jazmin M.; Hernández-Damián, Jacqueline; Pedraza-Chaverri, José

doi:10.1016/j.cellsig.2014.08.019

Cited by 1,091Autophagy in Disease and TherapyPI3K/AKT/mTOR signaling in cancerAlzheimer's disease research and treatments

The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration

Heras-Sandoval, David, Pérez-Rojas, Jazmin M., Hernández-Damián, Jacqueline, Pedraza-Chaverri, José·2014·Cellular Signalling

DOI 10.1016/j.cellsig.2014.08.019

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Abstract

Disruption of autophagy plays an import role in neurodegenerative disorders, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. Upstream of mTOR the survival PI3K/AKT pathway modulates mTOR activity that is also altered in neurodegenerative diseases of Alzheimer and Parkinson. Nevertheless, the interplay between the PI3K/AKT/mTOR pathway and the autophagic process is complex and a more detailed examination of tissue from patients suffering neurodegenerative diseases and of animal and cellular models is needed. In the present work we review the recent findings on the role of the PI3K/AKT/mTOR pathway in the modulation of the autophagic process in neuronal protection.

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Enhancing autophagy has previously been explored as a strategy to modulate neurodegeneration disease progression but with a focus on autophagic degradation of proteins, as opposed to autophagic degradation of intracellular LDs (lipophagy).
“Enhancing autophagy has previously been explored as a strategy to modulate neurodegeneration disease progression but with a focus on autophagic degradation of proteins41, as opposed to the autophagic degradation of intracellular LDs (lipophagy).”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [41]
Molecular and histopathologic analyses of patient tissues demonstrate mislocalized or accumulated autophagy machinery, pathogenic mutations underlying familial neurodegenerative diseases disable known autophagy-related factors, and genetically ablating autophagy effectors produces neurodegeneration in cell and animal model systems, supporting a role for autophagy dysfunction in age-related neurode
“Molecular and histopathologic analyses of patient tissues demonstrate mislocalized or accumulated autophagy machinery, pathogenic mutations underlying familial neurodegenerative diseases disable known autophagy-related factors, and genetically ablating autophagy effectors produce neurodegeneration in cell and animal model systems [74–81], supporting a role for autophagy dysfunction in the devel”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [77]

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Authors: Heras-Sandoval, D., Pérez-Rojas, J. M., Hernández-Damián, J., & Pedraza-Chaverri, J.
Affiliations: Universidad Nacional Autónoma de México (MX)
Venue: Cellular Signalling
Publisher: Elsevier BV
Published: 2014-12
Volume: 26
Issue: 12
Pages: 2694-2701
ISSN: 0898-6568 (ISSN-L)
DOI: 10.1016/j.cellsig.2014.08.019
OpenAlex: W2071466153
Cited by: 1,091
References: 108
Citations by year: 2026: 42 · 2025: 97 · 2024: 115 · 2023: 101 · 2022: 113 · 2021: 132 · 2020: 114 · 2019: 116 · 2018: 96 · 2017: 73 · 2016: 41 · 2015: 42 · 2014: 5 · 2013: 1
FWCI: 7.16
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cellular Signalling (publishedVersion)
PubMed (publishedVersion)
Funders: DGAPA-UNAM
PAPIIT (IN210713)
Topics: Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: PI3K/AKT/mTOR pathway, autophagy, protein aggregates, neurodegeneration, mTOR, neuronal survival, Alzheimer's disease, Parkinson's disease, autophagy regulation, cellular stress
MeSH terms: Animals, Autophagy, Humans, Neurons, Signal Transduction, Neurodegenerative Diseases, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases, Protein Aggregates

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The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration

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