Protein research may hint at how human eggs survive for decades DOI Creative Commons

Christina Szalinski

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)

Published: Oct. 23, 2024

Exposure to brighter nights and darker days causes circadian disruption, which accompanies poor health outcomes that increase mortality risk. Whether personal day night light exposure predicts risk is not known. This study ...Light enhances or disrupts rhythms, depending on the timing of exposure. Circadian disruption contributes has been established. We ...

Language: Английский

Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan DOI Creative Commons
Ewa Bomba-Warczak, Karen M Velez, Luhan T. Zhou

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 25, 2024

The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries gametes across lifespan. Ovaries exhibit localized structural cell-type-specific enrichment both follicular extrafollicular environments. Moreover, oocytes harbor panel long-lived including cytoskeletal, mitochondrial, oocyte-derived proteins. exceptional persistence these molecules suggest critical role lifelong maintenance age-dependent tissues.

Language: Английский

Citations

6
Sustained fertility from first-wave follicle oocytes that pause their growth DOI Creative Commons
Bikem Soygur, Eliza A. Gaylord, Mariko H. Foecke

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Ovulation results from the cyclical recruitment of non-renewing, quiescent oocytes for growth. Therefore, primordial follicles that are established during development an oocyte encapsulated by granulosa cells thought to comprise lifelong ovarian reserve

Language: Английский

Citations

2
Hallmarks of female reproductive aging in physiologic aging mice DOI
Julia L. Balough, Shweta S. Dipali, Karen M Velez

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(12), P. 1711 - 1730

Published: Dec. 13, 2024

Language: Английский

Citations

2
Levetiracetam prevents Aβ42 production through SV2a-dependent modulation of App processing in Alzheimer's disease models DOI Creative Commons
Nalini R. Rao,

Olivia DeGulis,

Toshihiro Nomura

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 28, 2024

Abstract In Alzheimer’s disease (AD), amyloid-beta (Aβ) peptides are produced by proteolytic cleavage of the amyloid precursor protein (APP), which can occur during synaptic vesicle (SV) cycling at presynapses. Precisely how amyloidogenic APP processing may impair presynaptic proteostasis and to therapeutically target this process remains poorly understood. Using App knock-in mouse models early Aβ pathology, we found proteins with hampered degradation accumulate sites. At mild pathological stage, leads accumulation 42 inside SVs. To explore if targeting SVs modulates accumulation, investigated levetiracetam (Lev), a SV-binding small molecule drug that has shown promise in mitigating AD-related pathologies despite its mechanism action being unclear. We discovered Lev reduces levels decreasing SV2a-dependent manner. corrects SV cycling, results increased surface localization APP, where it favors via non-amyloidogenic pathway. metabolic stable isotopes mass spectrometry confirmed prevents production vivo. transgenic mice aggressive electrophysiological immunofluorescent microscopy analyses revealed treatment minimizes synapse loss. Finally, human Down syndrome brains have elevated proteins, confirming comparable deficit brains. Taken together, report highlights therapeutic potential modify stages AD represent promising strategy prevent pathology before irreversible damage occurs. One Sentence Summary modulating alters thus processing, highlighting for AD.

Language: Английский

Citations

1
Switching on lysosomes DOI Creative Commons
Deepak Adhikari, John Carroll

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Aug. 21, 2024

The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.

Language: Английский

Citations

0
Protein research may hint at how human eggs survive for decades DOI Creative Commons

Christina Szalinski

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)

Published: Oct. 23, 2024

Exposure to brighter nights and darker days causes circadian disruption, which accompanies poor health outcomes that increase mortality risk. Whether personal day night light exposure predicts risk is not known. This study ...Light enhances or disrupts rhythms, depending on the timing of exposure. Circadian disruption contributes has been established. We ...

Language: Английский

Citations

0