Astragaloside IV mediates radiation-induced neuronal damage through activation of BDNF-TrkB signaling

Phytomedicine, Journal Year: 2024, Volume and Issue: 132, P. 155803 - 155803

Published: June 12, 2024

Language: Английский

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GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 11, 2024

Abstract Impaired ion channels regulating Golgi pH lead to structural alterations in the apparatus, such as fragmentation, which is found, along with cognitive impairment, Alzheimer’s disease. However, causal relationship between altered structure and impairment remains elusive due lack of understanding apparatus brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed astrocytes neurons contributes hippocampus-dependent memory. We find GolpHCat displays unique voltage-dependent currents, potently inhibited by gluconate. Additionally, gain insights into conduction through at molecular level determining three high-resolution cryogenic-electron microscopy structures human GolpHCat. GolpHCat-knockout mice show fragmented morphology glycosylation functions hippocampus, leading impaired spatial These findings suggest target for Golgi-related diseases impairment.

Language: Английский

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Cerebral Hypoxia-Induced Molecular Alterations and Their Impact on the Physiology of Neurons and Dendritic Spines: A Comprehensive Review

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Aug. 6, 2024

This article comprehensively reviews how cerebral hypoxia impacts the physiological state of neurons and dendritic spines through a series molecular changes, explores causal relationship between these changes neuronal functional impairment. As severe pathological condition, can significantly alter morphology function spines. Specifically, spines, being critical structures for to receive information, undergo such as reduction in number morphological abnormalities under hypoxic conditions. These alterations further affect synaptic function, leading neurotransmission disorders. delves into roles pathways like MAPK, AMPA receptors, NMDA BDNF hypoxia-induced outlines current treatment strategies. Neurons are particularly sensitive hypoxia, with their apical dendrites vulnerable damage, thereby affecting cognitive function. Additionally, astrocytes microglia play an indispensable role protecting structures, regulating normal functions, contributing repair process following injury. studies not only contribute understanding pathogenesis related neurological diseases but also provide important insights developing novel therapeutic Future research should focus on dynamic conditions intrinsic connections

Language: Английский

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The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for Hereditary Spastic Paraplegia

Progress in Neurobiology, Journal Year: 2024, Volume and Issue: 234, P. 102575 - 102575

Published: Jan. 26, 2024

Language: Английский

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hiPSC-Driven Organoid Construction and Application Prospects

Regenerative medicine and dentistry., Journal Year: 2025, Volume and Issue: unknown, P. 5 - 5

Published: March 21, 2025

Perspective hiPSC-Driven Organoid Construction and Application Prospects Bangheng Liu 1,2, Yulei Mu 2,3 Dong-An Wang 1,2,* 1 Department of Biomedical Engineering, Chinese University Hong Kong, Sha Tin, New Territories, Kong SAR 999077, China 2 Center for Neuromusculoskeletal Restorative Medicine, InnoHK, HKSTP, 3 City 83 Tat Chee Avenue, Kowloon, * Correspondence: [email protected] Received: 5 March 2025; Revised: 19 Accepted: 20 Published: 21 2025 Abstract: Induced pluripotent stem cell (iPSC)-derived organoid platforms can simulate various target tissues hold broad application prospects in personalized medicine, disease modeling, drug screening, organ transplantation, understanding development mechanisms. Currently, the human iPSC (hiPSC) organoids is gradually shifting towards Matrigel-free scaffold-free systems, promoting precise control over composition structure these systems establishing induction protocols specialized organoids. Researchers are also exploring construction multifunctional with complex structures material exchange channels through vascularization, segmented induction, assembly technologies, though further breakthroughs needed. In future, hiPSC expected to advance precision treatment, high-throughput module detection multi-organ integration, automation. Additionally, when combined large artificial intelligence models, there potential establish data medical platforms, providing support clinical decision-making. Moreover, AI anticipated foster collaboration rather than competition, coordinated growth field. For hiPSC-derived it crucial enhance ethical review framework balance radical scientific exploration conservative public attitudes. must optimize or develop new reduce genomic instability tumorigenic risks, while avoiding emergence non-target cells insufficient functional maturity.

Language: Английский

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Organelle perturbation in Alzheimer’s disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 15, 2025

Alzheimer’s disease is a devastating and incurable neurological disease. Most of the current research has focused on developing drugs to clear extracellular amyloid plaques in brain patients. However, this approach limited as it does not treat underlying cause In review, we highlight evidence field showing that accumulation intracellular toxic amyloid-ß could underpin very early events neuronal death both familial early-onset sporadic late-onset alzheimer’s Indeed, amyloid-ß, which produced within compartments, been shown perturb endosomal secretory organelles, different models, patients, leading membrane trafficking defects perturbation function associated with cognition defects. The Golgi apparatus central transport signaling hub at crossroads endocytic pathways ribbon structure hallmark Here, discuss role major player regulation amyloid-β production propose plays key cellular network can seed onset Moreover, an feedback loop enhanced level resulting before appearance clinical symptoms. Further advances defining molecular support design new therapeutic strategies target primary source toxicity

Language: Английский

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Neuromelanin and selective neuronal vulnerability to Parkinson’s disease

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Neuromelanin is a unique pigment made by some human catecholamine neurons. These neurons survive with their neuromelanin content for lifetime but can also be affected age-related neurodegenerative conditions, as observed using new imaging techniques. The limited quantities of has understanding its normal biology difficult, recent rodent and primate models, well omics studies, have confirmed importance selective neuronal loss in Parkinson's disease (PD). We review the development dopamine versus noradrenaline focus on previously overlooked cellular organelles formation function. discuss role stimulating endogenous α-synuclein misfolding PD which renders granules vulnerable, exacerbates other pathogenic processes.

Language: Английский

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Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109631 - 109631

Published: March 28, 2024

Psychedelics, recognized for their impact on perception, are resurging as promising treatments with rapid onset mood and substance use disorders. Despite increasing evidence from clinical trials, questions persist about the cellular molecular mechanisms precise correlation treatment outcomes. Murine neurons immortalized non-neural cell lines harboring overexpressed constructs have shed light neuroplastic changes mediated by serotonin 2A receptor (5-HT2AR) primary mechanism. However, limitations exist in capturing human- disease-specific traits. Here, we discuss current accomplishments prospects incorporating human pluripotent stem cells (PSCs) to complement these models. PSCs can differentiate into various brain types, mirroring endogenous expression patterns identities recreate disease phenotypes. Brain organoids derived resemble diversity patterning, while region-specific simulate circuit-level PSC-based models hold significant promise illuminate substrates of psychedelic-induced phenotypic recovery neuropsychiatric

Language: Английский

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Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot–Marie–Tooth 2B Disease

Biomolecules, Journal Year: 2023, Volume and Issue: 13(9), P. 1399 - 1399

Published: Sept. 16, 2023

Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of cellular signaling pathways that emanate from activated growth factor receptors after endocytosis. Endosomal trafficking, sorting, motility are coordinated by activity small GTPases, including Rab proteins, whose function as molecular switches direct at membranes through effector proteins. Rab7 is particularly important in coordination degradative functions pathway. effectors control maturation properties late lysosomal compartments, such recycling, motility, fusion with downstream compartments. The spatiotemporal regulation receptor challenging neurons because their enormous size, distinct intracellular domains unique requirements (dendrites vs. axons), long lifespans postmitotic, differentiated cells. In Charcot–Marie–Tooth 2B disease (CMT2B), familial missense mutations cause alterations GTPase cycling leading to an ulcero-mutilating peripheral neuropathy. prevailing hypothesis account for CMT2B pathologies CMT2B-associated alleles alter endocytic neurotrophin NGF its TrkA and, thereby, disrupt normal trophic nervous system, other Rab7-dependent impacted. Here, using a prototypical cargo, we review physiologic interactions neurons. Since among largest cells body, place particular emphasis on temporal spatial sorting neuronal processes. We further discuss current findings mutant models, impact or balance, how this dysregulation may confer disease.

Language: Английский

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Advances in understanding the roles of actin scaffolding and membrane trafficking in dendrite development

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2024, Volume and Issue: 51(11), P. 1151 - 1161

Published: June 24, 2024

Language: Английский

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