| 1. |
- Song, Lin, et al.
(författare)
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KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nanosized membrane vesicles released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) and play important roles in intercellular communication and numerous biological processes. However, the molecular mechanisms regulating exosome secretion remain poorly understood. Here we identify KIBRA as an adaptor-like protein that stabilizes Rab27a, which in turn controls exosome secretion both in vitro and in vivo. Knockdown or overexpression of KIBRA in neuronal and podocyte cell lines leads to a decrease or increase of exosome secretion, respectively, and KIBRA depletion increases MVB size and number. Comparing protein profiles between KIBRA knockout and wild-type mouse brain showed significantly decreased Rab27a, a small GTPase that regulates MVB-PM docking. Rab27a is stabilized by interacting with KIBRA, which prevents ubiquitination and degradation via the ubiquitin-proteasome pathway. In conclusion, we show that KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a.
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| 2. |
- Wang, Yongxiang, et al.
(författare)
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Lifespan Intellectual Factors, Genetic Susceptibility, and Cognitive Phenotypes in Aging : Implications for Interventions
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365 .- 1663-4365. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Along with rapid global population aging, the age-related cognitive disorders such as mild cognitive impairment (MCI) and dementia have posed a serious threat to public health, health care system, and sustainable economic and societal development of all countries. In this narrative review, we seek to summarize the major epidemiological studies from the life-course perspective that investigate the influence of genetic susceptibility [e.g., apolipoprotein (APOE) epsilon 4 allele] and intellectual or psychosocial factors (e.g., educational attainments and leisure activities) as well as their interactions on cognitive phenotypes in aging. Numerous population-based studies have suggested that early-life educational attainments and socioeconomic status, midlife work complexity and social engagements, late-life leisure activities (social, physical, and mentally-stimulating activities), certain personality traits (e.g., high neuroticism and low conscientiousness), and depression significantly affect late-life cognitive phenotypes. Furthermore, certain intellectual or psychosocial factors (e. g., leisure activities and depression) may interact with genetic susceptibility (e.g., APOE epsilon 4 allele) to affect the phenotypes of cognitive aging such that risk or beneficial effects of these factors on cognitive function may vary by carrying the susceptibility genes. Current evidence from the randomized controlled trials that support the cognitive benefits of cognitive training among cognitive healthy older adults remains limited. The cognitive reserve hypothesis has been proposed to partly explain the beneficial effects of lifetime intellectual and psychosocial factors on late-life cognitive function. This implies that, from a life-course perspective, preventive intervention strategies targeting multiple modifiable intellectual and psychosocial factors could interfere with clinical expression of cognitive disorders in old age and delay the onset of dementia syndrome, and thus, may help achieve healthy brain aging.
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