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Synthetic Activators of Autophagy

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Abstract

Autophagy is a central process for degradation of intracellular components that do not operate correctly. Molecular mechanisms underlying this process are extremely difficult to study, since they involve a large number of participants. The main task of autophagy is redistribution of cellular resources in response to environmental changes, such as starvation. Recent studies show that autophagy regulation could be the key to achieve healthy longevity, as well as to create therapeutic agents for treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Thus, development of autophagy activators with established detailed mechanism of action is a really important area of research. Several commercial companies are at various stages of development of such molecules, and some of them have already begun to introduce autophagy activators to the market.

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Fig. 1.
Fig. 2.

Abbreviations

Akt:

RAC-α serine/threonine protein kinase

AMPK:

AMP-activated protein kinase

BECN1:

beclin-1

FCCP:

carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone

FDA:

US Food and Drug Administration

LC3:

microtubule-associated protein light chain 3

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mTOR:

mammalian target of rapamycin

mTORC1:

mammalian target of rapamycin complex 1

p62/SQSTM1:

sequestosome 1

PI3K:

phosphatidylinositol-3-kinase

PIK3C3:

phosphatidylinositol 3-kinase catalytic subunit type 3

PINK1:

PTEN-induced protein kinase 1

PPAR:

peroxisome proliferator-activated receptors

ROS:

reactive oxygen species

SIRT1:

sirtuin 1

TFEB:

transcription factor EB

ULK1:

unc-51-like autophagy-activating kinase 1

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Acknowledgments

The authors are grateful to the members of research team, and to academicians A. G. Gabibov and A. A. Makarov for fruitful discussions.

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This work was financially supported by EFKO company.

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    Authors and Affiliations

    1. Center of Life Sciences, Skolkovo Institute of Science and Technology, 143025, Skolkovo, Russia

      Ekaterina A. Guseva, Julia A. Pavlova, Olga A. Dontsova & Petr V. Sergiev

    2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

      Ekaterina A. Guseva, Julia A. Pavlova, Olga A. Dontsova & Petr V. Sergiev

    3. Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

      Ekaterina A. Guseva, Julia A. Pavlova, Olga A. Dontsova & Petr V. Sergiev

    4. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, 117997, Moscow, Russia

      Olga A. Dontsova

    5. Institute of Functional Genomics, Lomonosov Moscow State University, 119991, Moscow, Russia

      Petr V. Sergiev

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    1. Ekaterina A. Guseva
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    E.A.G. and Yu.A.P. writing text of the paper, O.A.D. discussion of the material, P.V.S. concept and supervision of the study, editing text of the paper.

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    Guseva, E.A., Pavlova, J.A., Dontsova, O.A. et al. Synthetic Activators of Autophagy. Biochemistry Moscow 89, 27–52 (2024). https://doi.org/10.1134/S0006297924010024

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