The role of cellular senescence in neurodegenerative diseases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021476" target="_blank" >RIV/62690094:18470/24:50021476 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62156489:43210/24:43925205 RIV/00179906:_____/24:10484193

Výsledek na webu

<a href="https://link.springer.com/article/10.1007/s00204-024-03768-5" target="_blank" >https://link.springer.com/article/10.1007/s00204-024-03768-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-024-03768-5" target="_blank" >10.1007/s00204-024-03768-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The role of cellular senescence in neurodegenerative diseases

Popis výsledku v původním jazyce

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer’s disease (AD) and Parkinson’sdisease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrixmetalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possesshigh expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activityin in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of β-amyloid and tau-proteintangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase andnuclear factor kappa B signaling attenuate β-amyloid load and prevent tau-protein tangle deposition, thereby improvingcognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associatedwith increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α,and IL-1β secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerableneuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggestingstrategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

Název v anglickém jazyce

The role of cellular senescence in neurodegenerative diseases

Popis výsledku anglicky

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer’s disease (AD) and Parkinson’sdisease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrixmetalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possesshigh expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated β-galactosidase activityin in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of β-amyloid and tau-proteintangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase andnuclear factor kappa B signaling attenuate β-amyloid load and prevent tau-protein tangle deposition, thereby improvingcognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associatedwith increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α,and IL-1β secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerableneuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggestingstrategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA23-05857S" target="_blank" >GA23-05857S: Alzheimerova nemoc a stárnutí: dokáží inhibitory mTOR zabít dvě mouchy jednou ranou?</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Archives of toxicology

ISSN

0340-5761

e-ISSN

1432-0738

Svazek periodika

98

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

16

Strana od-do

2393-2408

Kód UT WoS článku

001222366500001

EID výsledku v databázi Scopus

2-s2.0-85192960748