International Immunopharmacology, Год журнала: 2024, Номер 141, С. 112940 - 112940
Опубликована: Авг. 17, 2024
Язык: Английский
Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)
Опубликована: Авг. 30, 2024
The primary challenge in today's world of neuroscience is the search for new therapeutic possibilities neurodegenerative disease. Central to these disorders lies among other factors, aberrant folding, aggregation, and accumulation proteins, resulting formation toxic entities that contribute neuronal degeneration. This review concentrates on key proteins such as β-amyloid (Aβ), tau, α-synuclein, elucidating intricate molecular events underlying their misfolding aggregation. We critically evaluate mechanisms governing elimination misfolded shedding light potential strategies. specifically examine pathways endoplasmic reticulum (ER) unfolded protein response (UPR), chaperones, chaperone-mediated autophagy (CMA), intersecting signaling Keap1-Nrf2-ARE, along with connected through p62. Above all, we emphasize significance quality control mechanisms, encompassing interventions targeting regulation post-translational modifications, enhancement chaperones clearance. Additionally, focus current new, multi-target approaches. In conclusion, this systematically consolidates insights into emerging strategies predicated aggregates
Язык: Английский
Процитировано
17
Journal of Clinical Medicine, Год журнала: 2024, Номер 13(2), С. 536 - 536
Опубликована: Янв. 17, 2024
Background: The concept of Alzheimer disease (AD)—since its histological discovery by to the present day—has undergone substantial modifications. Methods: We conducted a classical narrative review this field with bibliography selection (giving preference Medline best match). Results: following subjects are reviewed and discussed: Alzheimer’s discovery, Kraepelin’s creation new that was rare condition until 1970′s, growing interest investment in AD as major killer society large elderly population second half 20th century, consolidation clinicopathological model, modern nosology based on dominant amyloid hypothesis among many others. In 21st development biomarkers has supported novel biological definition AD, although proposed therapies have failed cure disease. incidence dementia/AD shown decrease affluent countries (possibly due control risk factors), mixed dementia been established most frequent etiology oldest old. Conclusions: current lacks unanimity. Many hypotheses attempt explain complex physiopathology entwined aging, cascade yielded poor therapeutic results. reduction appears promising but it should be confirmed future. A reevaluation is also necessary.
Язык: Английский
Процитировано
10
Fluids and Barriers of the CNS, Год журнала: 2025, Номер 22(1)
Опубликована: Янв. 9, 2025
Blood–brain barrier dysfunction is one characteristic of Alzheimer's disease (AD) and recognized as both a cause consequence the pathological cascade leading to cognitive decline. The goal this study was assess markers for in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at time autopsy determine what extent these are associated neuropathologic changes (ADNC) impairment. We used brain plasma 19 participants: 9 CNI 10 dementia patients had come University Kentucky Research Center (UK-ADRC) community-based cohort; all cases confirmed severe ADNC. Plasma obtained within 2 years autopsy. Aβ40, Aβ42, tau levels quantified by ELISA. Cortical sections cleared using X-CLARITY™ system immunostained neurovascular unit-related proteins. Brain slices then imaged confocal microscopy analyzed microvascular diameters immunoreactivity coverage Fiji/ImageJ. Isolated human microvessels assayed tight-junction protein expression JESS™ automated Western blot system. S100 calcium-binding B (S100β), matrix metalloproteinase (MMP)-2, MMP-9, neuron-specific enolase (NSE) All outcomes assessed linear associations global function (MMSE, CDR) cerebral atrophy scores Pearson, polyserial, polychoric correlation, appropriate, along generalized modeling mixed-level modeling. As expected, we detected elevated Aβ pathology compared CNI. However, found no differences sections. also observed claudin-5 capillaries isolated samples. biomarker analysis showed that 12.4-fold higher S100β levels, twofold lower NSE 2.4-fold MMP-9 1.2-fold MMP-2 than Data revealed predictive Our data suggest among different relevant dysfunction, most promising diagnostic Further investigation necessary how relate whether they may predict clinical outcomes, particularly prodromal early stages AD.
Язык: Английский
Процитировано
1
Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2025, Номер 11(1)
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1
Ageing Research Reviews, Год журнала: 2023, Номер 92, С. 102098 - 102098
Опубликована: Окт. 30, 2023
Язык: Английский
Процитировано
16
Chinese Journal of Natural Medicines, Год журнала: 2024, Номер 22(8), С. 699 - 710
Опубликована: Авг. 1, 2024
Язык: Английский
Процитировано
7
Materials Today Chemistry, Год журнала: 2024, Номер 40, С. 102222 - 102222
Опубликована: Июль 24, 2024
Язык: Английский
Процитировано
6
Journal of Clinical Medicine, Год журнала: 2024, Номер 13(3), С. 806 - 806
Опубликована: Янв. 30, 2024
Dementia is a major cause of poor quality life, disability, and mortality in old age. According to the geroscience paradigm, mechanisms that drive aging process are also involved pathogenesis chronic degenerative diseases, including dementia. The dissection such therefore instrumental providing biological targets for interventions new sources biomarkers. Within several biomarkers have been discovered can be measured blood allow early identification individuals at risk cognitive impairment. Examples markers include inflammatory biomolecules, neuroaxonal damage, extracellular vesicles, DNA methylation. Furthermore, gait speed, usual fast pace as part dual task, has shown detect future Here, we provide an overview available may used gauge impairment apparently healthy older adults. Further research should establish which combination possesses highest predictive accuracy toward incident implementation currently large share at-risk whom preventive implemented maintain or increase reserves, thereby reducing progression
Язык: Английский
Процитировано
5
Ageing Research Reviews, Год журнала: 2024, Номер 100, С. 102439 - 102439
Опубликована: Июль 27, 2024
Язык: Английский
Процитировано
5
Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102685 - 102685
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0