Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke DOI Creative Commons
Mengke Zhao, Jiayi Wang,

Shuaiyu Zhu

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 5, 2025

Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary promise of exosomes derived from human neural stem cells (hNSCs) management central nervous system (CNS) diseases. Nonetheless, precise mechanisms by which these target mitochondria to ameliorate effects IS remain only partially elucidated. This study investigates protective hNSC (hNSC-Exos) on damage. Using rat model middle cerebral artery occlusion (MCAO) vivo and OS-induced HT22 vitro. Firstly, our research group independently isolated subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored blood flow perfusion simulate ischemia-reperfusion injury, hNSC-Exos injected through stereotaxic injection into brain. Subsequently, evaluated, including histological studies, behavioral assessments. H2O2 was used OS environment MCAO, then its evaluated co-culturing with hNSC-Exos, immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). process exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) detect potential induction mitophagy cells. Afterwards, employed series mitochondrial function assessments autophagy related detection techniques, measuring membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) mCherry-GFP-LC3B staining. addition, further investigated regulatory pathway using inhibitor mdivi-1 knocking out PTEN induced kinase 1 (PINK1) Administration significantly ameliorated brain tissue damage enhanced outcomes rats. treatment led reduction apoptosis facilitated normalization impaired neurogenesis neuroplasticity. Notably, application vitro resulted an upregulation cells, thereby remedying dysfunction. We demonstrate that activate via PINK1/Parkin pathway, improving reducing apoptosis. These findings suggest alleviate regulating pathway. reveals novel cell-derived therapy promoting neuroprotection their as approach for OS-associated CNS diseases, IS.

Язык: Английский

Health benefits of resveratrol: Evidence from clinical studies DOI
Akhand Pratap Singh, R. P. Singh, Sumit Singh Verma

и другие.

Medicinal Research Reviews, Год журнала: 2019, Номер 39(5), С. 1851 - 1891

Опубликована: Фев. 11, 2019

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented over 244 clinical trials, with an additional 27 trials currently ongoing. Resveretrol reported to potentially improve the therapeutic outcome patients suffering from diabetes mellitus, obesity, colorectal cancer, breast multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney inflammatory rhinopharyngitis. polyphenol be safe at doses up 5 g/d, when used either alone or as combination therapy. molecular basis for are based on its ability modulate cell signaling molecules such cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor factor-binding 3, Ras association domain family pAkt, endothelial factor, cyclooxygenase 2, erythroid 2 like Kelch-like ECH-associated 1. Although utility well documented, rapid metabolism poor bioavailability limited use. In this regard, recently produced micronized formulation called SRT501, shows promise. This review discusses available data prevention, management, treatment various diseases disorders. Based current evidence, potential molecule clinic discussed.

Язык: Английский

Процитировано

424
AMPK: Potential Therapeutic Target for Ischemic Stroke DOI Creative Commons
Shuai Jiang, Tian Li,

Ting Ji

и другие.

Theranostics, Год журнала: 2018, Номер 8(16), С. 4535 - 4551

Опубликована: Янв. 1, 2018

5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine (Ser/Thr) group, is universally distributed in various cells and organs.It significant endogenous defensive molecule that responds to harmful stimuli, such as cerebral ischemia, hemorrhage, and, neurodegenerative diseases (NDD).Cerebral which results from insufficient blood flow or blockage vessels, major cause ischemic stroke.Ischemic stroke has received increased attention due its '3H' effects, namely high mortality, morbidity, disability.Numerous studies have revealed activation AMPK plays protective role brain, whereas action remains elusive poorly understood.Based on existing evidence, we introduce basic structure, upstream regulators, biological roles AMPK.Second, analyze relationship between neurovascular unit (NVU).Third, actions different phases ischemia current therapeutic methods are discussed.Finally, evaluate controversy provide detailed analysis, followed by ethical issues, potential directions, further prospects AMPK.The information complied here may aid clinical research AMPK, be potent drug candidate for treatment future.

Язык: Английский

Процитировано

203
Role of autophagy in di-2-ethylhexyl phthalate (DEHP)-induced apoptosis in mouse Leydig cells DOI

Ying-Yin Sun,

Jingcao Shen,

Lin Zeng

и другие.

Environmental Pollution, Год журнала: 2018, Номер 243, С. 563 - 572

Опубликована: Сен. 5, 2018

Язык: Английский

Процитировано

118
Dual Role of Autophagy in Diseases of the Central Nervous System DOI Creative Commons

Tamara Bar-Yosef,

Odeya Damri,

Galila Agam

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2019, Номер 13

Опубликована: Май 28, 2019

Autophagy is a vital lysosomal degradation and recycling pathway in the eukaryotic cell, responsible for maintaining an intricate balance between cell survival death, necessary neuronal function. This dual role played by autophagy raises question whether this process protective or destructive pathway, contributor of death failed attempt to repair aberrant processes? De-regulated at different steps excessive downregulated, has been proposed be associated with neurodegenerative disorders such as Alzheimer's-, Huntington's- Parkinson's-disease, known their intracellular accumulation protein aggregates. Recent observations impaired also appeared psychiatric schizophrenia bipolar disorder suggesting additional contribution pathophysiology mental illness. Here we review current understanding autophagy's various neuropsychiatric and, hitherto, prevailing new potential autophagy-related therapeutic strategies treatment.

Язык: Английский

Процитировано

116
Autophagy and apoptosis cascade: which is more prominent in neuronal death? DOI

Rohan Gupta,

Rashmi K. Ambasta, Pravir Kumar

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2021, Номер 78(24), С. 8001 - 8047

Опубликована: Ноя. 6, 2021

Язык: Английский

Процитировано

104
Advance of sporadic Alzheimer's disease animal models DOI
Lili Zhang, Chen Chen,

Marvin SH Mak

и другие.

Medicinal Research Reviews, Год журнала: 2019, Номер 40(1), С. 431 - 458

Опубликована: Июль 22, 2019

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disease. In past decades, numbers promising drug candidates showed significant anti-AD effects in preclinical studies but failed clinical trials. One major reasons might be limitation appropriate animal models for evaluating drugs. More than 95% AD cases are sporadic (sAD). However, were mainly tested familial (fAD) models. The diversity between sAD and fAD lead to high failure rate during development Therefore, an ideal model urgently needed Here, we summarized available models, including their methodology, pathologic features, potential underlying mechanisms. limitations these future trends field also discussed.

Язык: Английский

Процитировано

94
Lipid peroxidation in neurodegeneration DOI
Carmen Peña‐Bautista, Máximo Vento,

Miguel Baquero

и другие.

Clinica Chimica Acta, Год журнала: 2019, Номер 497, С. 178 - 188

Опубликована: Авг. 1, 2019

Язык: Английский

Процитировано

85
Zinc in Cognitive Impairment and Aging DOI Creative Commons
Ruize Sun, Jue Wang, Juan Feng

и другие.

Biomolecules, Год журнала: 2022, Номер 12(7), С. 1000 - 1000

Опубликована: Июль 18, 2022

Zinc, an essential micronutrient for life, was first discovered in 1869 and later found to be indispensable the normal development of plants growth rats birds. Zinc plays important role many physiological pathological processes mammalian brain development, especially central nervous system. deficiency can lead neurodegenerative diseases, mental abnormalities, sleep disorders, tumors, vascular other conditions, which cause cognitive impairment premature aging. This study aimed review effects zinc zinc-associated proteins aging, reveal its molecular mechanism, highlight potential interventions aging impairments.

Язык: Английский

Процитировано

44
Genetic Phenotypes of Alzheimer’s Disease: Mechanisms and Potential Therapy DOI Creative Commons
Meina Quan, Shuman Cao, Qi Wang

и другие.

Phenomics, Год журнала: 2023, Номер 3(4), С. 333 - 349

Опубликована: Апрель 3, 2023

Abstract Years of intensive research has brought us extensive knowledge on the genetic and molecular factors involved in Alzheimer's disease (AD). In addition to mutations three main causative genes familial AD (FAD) including presenilins amyloid precursor protein genes, studies have identified several as most plausible for onset progression FAD, such triggering receptor expressed myeloid cells 2 , sortilin-related 1 adenosine triphosphate-binding cassette transporter subfamily A member 7 . The apolipoprotein E ε4 allele is reported be strongest risk factor sporadic (SAD), it also plays an important role FAD. Here, we reviewed recent developments that contributed understanding phenotypes FAD compared them with SAD. We further advancements gene therapy discussed future perspectives based phenotypes.

Язык: Английский

Процитировано

35
Endoplasmic reticulum stress-mediated cell death in cardiovascular disease DOI Creative Commons

Yajuan An,

Xinshuang Wang,

Xiuju Guan

и другие.

Cell Stress and Chaperones, Год журнала: 2024, Номер 29(1), С. 158 - 174

Опубликована: Янв. 29, 2024

The endoplasmic reticulum (ER) plays a vital function in maintaining cellular homeostasis. Endoplasmic stress (ERS) can trigger various modes of cell death by activating the unfolded protein response (UPR) signaling pathway. Cell crucial role occurrence and development diseases such as cancer, liver diseases, neurological cardiovascular diseases. Several including hypertension, atherosclerosis, heart failure are associated with ER stress. stress-mediated is interest disease. Moreover, an increasing body evidence supports potential modulating ERS for treating This paper provides comprehensive review UPR pathway, mechanisms that induce death, Additionally, we discuss common along therapeutic strategies.

Язык: Английский

Процитировано

15