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Article

Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes

by
Nina Kraskovskaya
1,
Natalia Linkova
2,*,†,
Elena Sakhenberg
1,
Daria Krieger
1,
Victoria Polyakova
2,†,
Dmitrii Medvedev
3,4,
Alexander Krasichkov
5,
Mikhail Khotin
1 and
Galina Ryzhak
3
1
Institute of Cytology RAS, Tikhoretski Pr., 4, St. Petersburg 194064, Russia
2
St. Petersburg Research Institute of Phthisiopulmonology, Ligovskii Pr., 2−4, St. Petersburg 191036, Russia
3
St. Petersburg Institute of Bioregulation and Gerontology, 3 Dynamo Ave., St. Petersburg 197110, Russia
4
The Department of Social Rehabilitation and Occupational Therapy, St. Petersburg Medical and Social Institute, Kondratievsky St., 72A, St. Petersburg 195271, Russia
5
Department of Radio Engineering Systems, Saint Petersburg Electrotechnical University ‘LETI’, 5F Prof. Popova St., St. Petersburg 197376, Russia
*
Author to whom correspondence should be addressed.
†
Current address: The Laboratory of Fundamental and Translational Aging Research, Institute of Experimental Medicine, Acad. Pavlov Street, 12, St. Petersburg 197022, Russia.
Int. J. Mol. Sci. 2024, 25(21), 11363; https://doi.org/10.3390/ijms252111363
Submission received: 18 September 2024 / Revised: 14 October 2024 / Accepted: 17 October 2024 / Published: 22 October 2024
(This article belongs to the Special Issue Natural Bioactive Molecules for the Management of Age-Related Disorders)
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Abstract

Neurons become more vulnerable to stress factors with age, which leads to increased oxidative DNA damage, decreased activity of mitochondria and lysosomes, increased levels of p16, decreased LaminB1 proteins, and the depletion of the dendritic tree. These changes are exacerbated in vulnerable neuronal populations during the development of neurodegenerative diseases. Glu-Asp-Arg (EDR) and Lys-Glu-Asp (KED), and Ala-Glu-Asp-Gly (AEDG) peptides have previously demonstrated neuroprotective effects in various models of Alzheimer’s disease. In this study, we investigated the influence of EDR, KED, and AEDG peptides on the aging of fibroblast-derived induced neurons. We used a new in vitro cellular model of human neuronal aging based on the transdifferentiation of aged dermal fibroblasts from elderly donors into induced cortical neurons. All peptides promote the arborization of the dendritic tree, increasing both the number of primary processes and the total length of dendrites. Tripeptides have no effect on the activity of mitochondria and lysosomes and the level of p16 protein in induced neurons. EDR peptide reduces oxidative DNA damage in induced neurons derived from elderly donor fibroblasts. Short peptides partially protect induced neurons from age-related changes and stimulate dendritogenesis in neurons. They can be recommended for use as neuroprotective agents.
Keywords: tripeptides; induced neurons; aging; oxidative DNA damage; dendrites; morphology; mitochondria; lysosomes; short peptides tripeptides; induced neurons; aging; oxidative DNA damage; dendrites; morphology; mitochondria; lysosomes; short peptides

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MDPI and ACS Style

Kraskovskaya, N.; Linkova, N.; Sakhenberg, E.; Krieger, D.; Polyakova, V.; Medvedev, D.; Krasichkov, A.; Khotin, M.; Ryzhak, G. Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes. Int. J. Mol. Sci. 2024, 25, 11363. https://doi.org/10.3390/ijms252111363

AMA Style

Kraskovskaya N, Linkova N, Sakhenberg E, Krieger D, Polyakova V, Medvedev D, Krasichkov A, Khotin M, Ryzhak G. Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes. International Journal of Molecular Sciences. 2024; 25(21):11363. https://doi.org/10.3390/ijms252111363

Chicago/Turabian Style

Kraskovskaya, Nina, Natalia Linkova, Elena Sakhenberg, Daria Krieger, Victoria Polyakova, Dmitrii Medvedev, Alexander Krasichkov, Mikhail Khotin, and Galina Ryzhak. 2024. "Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes" International Journal of Molecular Sciences 25, no. 21: 11363. https://doi.org/10.3390/ijms252111363

APA Style

Kraskovskaya, N., Linkova, N., Sakhenberg, E., Krieger, D., Polyakova, V., Medvedev, D., Krasichkov, A., Khotin, M., & Ryzhak, G. (2024). Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes. International Journal of Molecular Sciences, 25(21), 11363. https://doi.org/10.3390/ijms252111363

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