iScience, Год журнала: 2023, Номер 27(1), С. 108745 - 108745
Опубликована: Дек. 19, 2023
Alzheimer's disease (AD) is characterized by peri-neuronal amyloid plaque and intra-neuronal neurofibrillary tangles. These aggregates are identified the immunodetection of "seed" proteins (Aβ
Язык: Английский
Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(2), С. 457 - 477
Опубликована: Март 12, 2024
Язык: Английский
Процитировано
32
Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16
Опубликована: Май 14, 2024
As the global population ages, incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that β-amyloid protein (Aβ) deposition is a key factor leading AD. However, clinical efficacy treating AD anti-Aβ antibodies not satisfactory, suggesting Aβ amyloidosis may be pathological change rather than Identification causes and development corresponding prevention treatment strategies an important goal current research. Following discovery soluble oligomeric forms (AβO) in 1998, scientists began focus on neurotoxicity AβOs. endogenous neurotoxin, active growth AβOs can lead neuronal death, which believed occur before plaque formation, are factors PANoptosis, newly proposed concept cell death includes known modes pyroptosis, apoptosis, necroptosis, form regulated PANoptosome complex. Neuronal survival depends proper mitochondrial function. Under conditions AβO interference, dysfunction occurs, releasing lethal contents as potential upstream effectors PANoptosome. Considering critical role neurons cognitive function well regulatory survival, investigation mechanisms PANoptosis crucial. This review describes disruption elucidates how activate causing during AD, providing guidance for targeted strategies.
Язык: Английский
Процитировано
8
Ageing Research Reviews, Год журнала: 2024, Номер 98, С. 102320 - 102320
Опубликована: Май 6, 2024
Aging is a gradual and irreversible natural process. With aging, the body experiences functional decline, effects amplify vulnerability to range of age-related diseases, including neurodegenerative, cardiovascular, metabolic diseases. Within aging process, morphology function mitochondria endoplasmic reticulum (ER) undergo alterations, particularly in structure connecting these organelles known as mitochondria-associated membranes (MAMs). MAMs serve vital intracellular signaling hubs, facilitating communication between ER when regulating various cellular events, calcium homeostasis, lipid metabolism, mitochondrial function, apoptosis. The formation partly dependent on interaction vesicle-associated membrane protein-associated protein-B (VAPB) protein tyrosine phosphatase-interacting protein-51 (PTPIP51). Accumulating evidence has begun elucidate pivotal role VAPB-PTPIP51 tether initiation progression In this study, we delineate intricate multifunctional discuss its profound implications aging-associated Moreover, provide comprehensive overview potential therapeutic interventions pharmacological agents targeting VAPB-PTPIP51-mediated MAMs, thereby offering glimmer hope mitigating processes treating disorders.
Язык: Английский
Процитировано
7
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12025 - 12025
Опубликована: Июль 27, 2023
Sigma (σ) receptors are a class of unique proteins with two subtypes: the sigma-1 (σ1) receptor which is situated at mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), and sigma-2 (σ2) receptor, located in ER-resident membrane. Increasing evidence indicates involvement both σ1 σ2 pathogenesis Alzheimer’s disease (AD), thus these represent potentially effective biomarkers for emerging AD therapies. The availability optimal radioligands positron emission tomography (PET) neuroimaging humans will provide tools to monitor progression treatment outcomes. In this review, we first summarize significance pathophysiology highlight therapeutic strategies related receptors. We then survey potential PET radioligands, an emphasis on requirements imaging or humans. Finally, discuss current challenges development receptors, opportunities elucidate as novel early diagnosis, monitoring drug efficacy.
Язык: Английский
Процитировано
15
Molecular Medicine, Год журнала: 2025, Номер 31(1)
Опубликована: Фев. 18, 2025
Abstract Abnormal glucose metabolism inevitably disrupts normal neuronal function, a phenomenon widely observed in Alzheimer’s disease (AD). Investigating the mechanisms of metabolic adaptation during progression has become central focus research. Considering that impaired is closely related to decreased insulin signaling and resistance, new concept "type 3 diabetes mellitus (T3DM)" been coined. T3DM specifically refers brain’s neurons becoming unresponsive insulin, underscoring strong link between AD. Recent studies reveal brain exhibit mitochondrial dysfunction, reduced metabolism, elevated lactate levels. These findings suggest caused by may lead compensatory shift toward glycolysis. Consequently, this review aims explore underlying causes elucidate how resistance drives reprogramming AD progression. Additionally, it highlights therapeutic strategies targeting sensitivity function as promising avenues for successful development treatments.
Язык: Английский
Процитировано
0
ACS Chemical Biology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 15, 2025
Flavonoids such as sterubin and fisetin─and derivatives thereof─show strong neuroprotective effects in vitro well vivo, combined with negligible toxicity can therefore be considered novel treatment options for neurodegenerative diseases Alzheimer's disease. However, their subcellular locations responsible neuroprotection exact modes of action still remain unclear. Here, we present chemical probes based on both flavonoids fisetin that were utilized fluorescence microscopy click-correlative light electron to detect visualize the localization specific intracellular targets. We successfully adapted workflow correlative a click-chemistry-based approach murine hippocampal cell line (HT22) ultrathin resin sections making visualization small molecule first time possible this setup. Utilizing newly technique, could demonstrate show enrichment endoplasmic reticulum.
Язык: Английский
Процитировано
0
Communications Biology, Год журнала: 2025, Номер 8(1)
Опубликована: Фев. 16, 2025
Cancer stem cells (CSCs) play crucial roles in cancer progression, immune evasion, drug resistance, and recurrence. Understanding the mechanisms behind CSCs generation stemness maintenance is vital for early diagnosis treatment. Here, we unveil that carnitine palmitoyltransferase 1A (CPT1A) highly expressed ovarian (OCSCs) essential maintaining by regulating lipid desaturation. Studies confirmed CPT1A enhances SREBP1 activation, upregulating SCD1 expression, promoting desaturation OCSCs. Mechanistic studies reveal promotes succinylation of mitochondrial fission factor (MFF) through its lysine succinyltransferase (LSTase) activity, mitochondria-associated membranes formation activation. Inhibiting CPT1A's LSTase activity with Glyburide reduces OCSCs' cisplatin's anti-tumor effects against vitro vivo. Together, our highlight significance stemness, offering potential targets therapeutic strategies Carnitine found to promote mediating succinylation.
Язык: Английский
Процитировано
0
Ageing Research Reviews, Год журнала: 2025, Номер unknown, С. 102713 - 102713
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Chemical Biology Letters, Год журнала: 2023, Номер 10(4)
Опубликована: Дек. 1, 2023
Neurodegenerative diseases, marked by the gradual deterioration of neuronal structure and function, impose a significant burden on global healthcare systems. Oxidative stress, resulting from an imbalance between reactive oxidant production cellular antioxidant defense, is believed to play role in development various neurodegenerative disorders, including Alzheimer's disease, Parkinson's Huntington's disease. Recently, there has been growing interest exploring small compounds as potential therapeutic agents counteract oxidative stress. In addition highlighting molecules prevent stress-mediated damage, this article provides overview function stress illnesses. Targeting numerous stress-related pathways, number molecules, both natural synthetic antioxidants, have shown promise for neuroprotective benefits. These substances neutralise oxidants, boost endogenous defences, reduce inflammation, alter mitochondrial encourage neurotrophic growth. URN:NBN:sciencein.cbl.2023.v10.626
Язык: Английский
Процитировано
8
Toxicology Reports, Год журнала: 2024, Номер 13, С. 101812 - 101812
Опубликована: Ноя. 13, 2024
Язык: Английский
Процитировано
2