Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases

David Heras-Sandoval, Jazmin M. Pérez-Rojas, José Pedraza-Chaverri

Research output: Contribution to journalReview article

Abstract

Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress 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. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer's disease (AD) and Parkinson's disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years.

Original languageEnglish (US)
Article number109442
JournalCellular Signalling
Volume65
DOIs
StatePublished - Jan 2020

Fingerprint

Phosphatidylinositol 3-Kinase
Curcumin
Autophagy
Sirolimus
Mitogen-Activated Protein Kinases
Neurodegenerative Diseases
Parkinson Disease
Alzheimer Disease
Proto-Oncogene Proteins c-akt
1-Phosphatidylinositol 4-Kinase
Poisons
Extracellular Signal-Regulated MAP Kinases
Starvation
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Neurons
Protein Aggregates
Beclin-1
mechanistic target of rapamycin complex 1
TOR complex 2

Keywords

  • Alzheimer's disease
  • Apelin
  • Autophagy
  • Beclin-1
  • Cubeben
  • Curcumin
  • Mammalian target of rapamycin complex
  • Mitogen activated protein kinases
  • Neurodegeneration
  • Parkinson's disease
  • Phosphatidylinositol-3-kinase

ASJC Scopus subject areas

  • Cell Biology

Cite this

Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases. / Heras-Sandoval, David; Pérez-Rojas, Jazmin M.; Pedraza-Chaverri, José.

In: Cellular Signalling, Vol. 65, 109442, 01.2020.

Research output: Contribution to journalReview article

@article{2729edaa925948a88cf49e86832e7122,
title = "Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases",
abstract = "Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress 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. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer's disease (AD) and Parkinson's disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years.",
keywords = "Alzheimer's disease, Apelin, Autophagy, Beclin-1, Cubeben, Curcumin, Mammalian target of rapamycin complex, Mitogen activated protein kinases, Neurodegeneration, Parkinson's disease, Phosphatidylinositol-3-kinase",
author = "David Heras-Sandoval and P{\'e}rez-Rojas, {Jazmin M.} and Jos{\'e} Pedraza-Chaverri",
year = "2020",
month = "1",
doi = "10.1016/j.cellsig.2019.109442",
language = "English (US)",
volume = "65",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases

AU - Heras-Sandoval, David

AU - Pérez-Rojas, Jazmin M.

AU - Pedraza-Chaverri, José

PY - 2020/1

Y1 - 2020/1

N2 - Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress 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. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer's disease (AD) and Parkinson's disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years.

AB - Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress 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. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer's disease (AD) and Parkinson's disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years.

KW - Alzheimer's disease

KW - Apelin

KW - Autophagy

KW - Beclin-1

KW - Cubeben

KW - Curcumin

KW - Mammalian target of rapamycin complex

KW - Mitogen activated protein kinases

KW - Neurodegeneration

KW - Parkinson's disease

KW - Phosphatidylinositol-3-kinase

UR - http://www.scopus.com/inward/record.url?scp=85074228659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074228659&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2019.109442

DO - 10.1016/j.cellsig.2019.109442

M3 - Review article

C2 - 31639492

AN - SCOPUS:85074228659

VL - 65

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

M1 - 109442

ER -