Harnessing BDNF Signaling to Promote Resilience in Aging DOI Open Access
Jamshid Faraji, Gerlinde A. S. Metz

Published: July 29, 2024

As a key member of the neurotrophin family in central nervous system, brain-derived neurotrophic factor (BDNF) plays critical role maintenance and plasticity system. Its innate neuroprotective advantage can also be shared with brain when normal aging-dependent processes challenge neural circuits. The intricate relationship between BDNF resilience during aging process signifies molecular mechanisms that underlie protection function, such as cognition, movement psychological well-being. is crucial for neuronal growth survival, it promote against age-related functional decline frailty, even if fails to entirely prevent ageing-related decline. In present review, we discuss function from perspective how may aging. We emphasize briefly principal, well-known cellular hallmarks restrict disabling dynamics enhance overall Insight into pathways through which reduces dysfunctions and/or improves resilience, provide foundation developing targeted interventions mental well-being an population.

Language: Английский

Single-cell multiregion dissection of Alzheimer’s disease DOI Creative Commons
Hansruedi Mathys, Carles A. Boix, Leyla Anne Akay

et al.

Nature, Journal Year: 2024, Volume and Issue: 632(8026), P. 858 - 868

Published: July 24, 2024

Abstract Alzheimer’s disease is the leading cause of dementia worldwide, but cellular pathways that underlie its pathological progression across brain regions remain poorly understood 1–3 . Here we report a single-cell transcriptomic atlas six different in aged human brain, covering 1.3 million cells from 283 post-mortem samples 48 individuals with and without disease. We identify 76 cell types, including region-specific subtypes astrocytes excitatory neurons an inhibitory interneuron population unique to thalamus distinct canonical subclasses. vulnerable populations are depleted specific disease, provide evidence Reelin signalling pathway involved modulating vulnerability these neurons. develop scalable method for discovering gene modules, which use cell-type-specific modules altered annotate differences associated diverse variables. astrocyte program cognitive resilience pathology, tying choline metabolism polyamine biosynthesis preserved function late life. Together, our study develops regional ageing provides insights into vulnerability, response pathology.

Language: Английский

Citations

57
Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee DOI
Joel N. Buxbaum, David Eisenberg, Marcus Fändrich

et al.

Amyloid, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 8

Published: Sept. 30, 2024

The ISA Nomenclature Committee met at the XIX International Symposium of Amyloidosis in Rochester, MN, 27 May 2024. in-person event was followed by many electronic discussions, resulting current updated recommendations. general nomenclature principles are unchanged. total number human amyloid fibril proteins is now 42 which 19 associated with systemic deposition, while 4 occur either localised or deposits. Most amyloidoses caused presence protein variants promote misfolding. However, cases AA and ATTR deposits most commonly consist wild-type and/or their fragments. One peptide drug, previously reported to create local iatrogenic its injection site, has been shown induce rare instances deposition. described animal 16, 2 unknown humans. Recognition importance intracellular aggregates, may have amyloid-like properties, neurodegenerative diseases rapidly increasing significance discussed.

Language: Английский

Citations

18
Efficient Gene Delivery Admitted by small Metabolites Specifically Targeting Astrocytes in the Mouse Brain DOI

Haibin Zhou,

Jiajing Dai,

Dong Li

et al.

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 1166 - 1179

Published: Jan. 11, 2025

Language: Английский

Citations

1
Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases DOI
Michal Izrael, Judith Chebath, Kfir Molakandov

et al.

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115525 - 115525

Published: Jan. 1, 2025

Language: Английский

Citations

1
The Glutamate/GABA‐Glutamine Cycle: Insights, Updates, and Advances DOI Creative Commons
Jens V. Andersen

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(3)

Published: March 1, 2025

ABSTRACT Synaptic homeostasis of the principal neurotransmitters glutamate and GABA is tightly regulated by an intricate metabolic coupling between neurons astrocytes known as glutamate/GABA‐glutamine cycle. In this cycle, take up from synapse convert these into glutamine. Astrocytic glutamine subsequently transferred to neurons, serving precursor for neuronal synthesis. The cycle integrates multiple cellular processes, including neurotransmitter release, uptake, synthesis, metabolism. All processes are deeply interdependent closely coupled energy Astrocytes display highly active mitochondrial oxidative metabolism several unique features, glycogen storage pyruvate carboxylation, which essential sustain continuous release. However, new roles oligodendrocytes microglia in recycling emerging. Malfunction can lead severe synaptic disruptions may be implicated brain diseases. Here, I review central aspects recent advances highlight how functionally connected critical functions First, overview glutamate, GABA, transport provided relation recycling. Then, reviewed, with a special emphasis on glial cells. Finally, discuss aberrant linked neurodegeneration disease, focusing astrocyte dysfunction lipid emerging pathological mechanisms. Instead viewing individual biochemical more holistic integrative approach needed advance our understanding modulates function both health disease. image

Language: Английский

Citations

1
Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators DOI Creative Commons
Alka Ashok Singh, Dhananjay Yadav, Fazlurrahman Khan

et al.

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 674 - 674

Published: July 2, 2024

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience action of antidepressant drugs, making them prominent targets psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, mental illnesses, exacerbates aging process. The nuclear erythroid 2-related 2 (Nrf2)-antioxidant responsive element (ARE) serves as primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection OS-related damage; notably, TrkB/phosphoinositide 3-kinase (PI3K)/protein (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates promotes translocation. However, insufficient neurotrophin support often leads downregulation diseases. targeting Nrf2-ARE system is a promising therapeutic strategy for treating Phytochemicals, indole-3-carbinol (I3C) metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF’s mimetic activity; Akt phosphorylation induced, antioxidant activated blocking Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes potential I3C derivatives concurrently activating neuronal mechanisms treatment

Language: Английский

Citations

7
Non-Immune Functions of Innate Immunity Acting on Physiological Processes: Insights from Drosophila DOI Open Access
Xiaoyan Li, Xiaomin Wang, Zhen Shang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1087 - 1087

Published: Jan. 27, 2025

As the first line of host immune defense, innate immunity plays a key role in warding off foreign pathogens and damage. Drosophila melanogaster, as classical model animal for more than 100 years, is an important research studying immunity. In recent scientists have made remarkable progress recognition mechanisms immunity, effector molecules, modes their response at cellular tissue levels. However, interaction between other physiological functions remains relatively novel has yet to be systematically explored. Here, we briefly discuss link system regulation, from several representative perspectives such sleep, insulin, brain function. Then, using model, provide overview specifically summarize on regulation physiology by covering lipid metabolism, development, neurodegenerative diseases, memory, feeding, lifespan, movement, antioxidation. This review provides valuable into how influences processes, providing deeper understanding complex roles underlying

Language: Английский

Citations

0
Brain‐Wide Neuroregenerative Gene Therapy Improves Cognition in a Mouse Model of Alzheimer's Disease DOI Creative Commons
Zheng Wu,

Liang Xu,

Yangli Xie

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Alzheimer's disease (AD) is a progressive and irreversible brain disorder with extensive neuronal loss in the neocortex hippocampus. Current therapeutic interventions focus on early stage of AD but lack effective treatment for late AD, largely due to inability replenish lost neurons repair broken neural circuits. In this study, by using engineered adeno-associated virus vectors that efficiently cross blood-brain-barrier mouse brain, brain-wide neuroregenerative gene therapy developed directly convert endogenous astrocytes into functional model AD. It found ≈500 000 new are regenerated widely distributed cerebral cortex Importantly, it demonstrated converted can integrate pre-existing networks improve various cognitive performances mice. Chemogenetic inhibition abolishes memory enhancement mice, suggesting pivotal role newly restoration. Together, may provide viable strategy other disorders associated massive loss.

Language: Английский

Citations

0
PLXNB1 and other signaling drives a pathologic astrocyte state contributing to cognitive decline in Alzheimer's Disease DOI Open Access
Natacha Comandante-Lou,

Tsering Lama,

Kevin W. Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Alzheimer's disease (AD) is marked by the coordinated emergence of disease-associated cell states across multiple types. Here, we first performed a meta-analysis single-nucleus transcriptomic (snRNAseq) data from 869 brains diverse decedents, confirming critical role an SLC38A2 high SMTN CACNA1D astrocyte subset, Astrocyte 10 (Ast10), in AD and aging-related cognitive decline. We then investigated signaling drivers Ast10's aging brain, focusing on interactions among microglial astrocytic subsets. Analysis snRNAseq prioritized set ligands receptors that are robustly predictive Ast10 proportions participants, confirm our predictions studies. Independent validation with spatial transcriptomics reveals striking colocalization these signature brain tissue, but not other states. Genetic ablation top receptor PLXNB1 murine human iPSC-derived astrocytes decreased signature, its regulatory role. Finally, find may contribute to decline through synaptic loss associated independent AD. Thus, regulators potential points convergence for neurodegenerative mechanisms be promising targets therapeutic development preserve function.

Language: Английский

Citations

0
Advances in Spatial Omics Technologies DOI
Tianqian Hui, Jian Zhou,

Ming Yao

et al.

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Rapidly developing spatial omics technologies provide us with new approaches to deeply understanding the diversity and functions of cell types within organisms. Unlike traditional approaches, enable researchers dissect complex relationships between tissue structure function at cellular or even subcellular level. The application provides perspectives on key biological processes such as nervous system development, organ tumor microenvironment. This review focuses advancements strategies technologies, summarizes their applications in biomedical research, highlights power advancing life sciences related development disease.

Language: Английский

Citations

0