Physical Exercise Counteracts Aging-Associated White Matter Demyelination Causing Cognitive Decline DOI Creative Commons

Tanya Butt,

Makoto Tobiume,

Diane B. Ré

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(5), P. 2136 - 2136

Published: Jan. 1, 2024

In the central nervous system, oligodendrocytes wrap around neuronal axons to form myelin, an insulating layer or sheath that allows for efficient conductance of action potentials. addition structural insulation, myelin provides encased with nutrient, metabolic and defensive support. Demyelination, loss, can therefore cause axonal dysfunction, leading neurological impairment disease. Alzheimer's disease (AD), progressive white matter demyelination is acknowledged as one earliest pathologies preceding symptom onset. Unfortunately, current pharmacotherapy slowing promoting remyelination in AD nonexistent. Exercise recognized its wide-ranging benefits human health, including improved mental health prevention lifestyle-related diseases. Mounting evidence suggests contribution physical activity delaying progression dementia elderly populations. Recent mechanistic studies have shown exercise facilitates myelination brain through vitalization intrinsic pro-myelination cues, such increased neurotrophic factors electrical activity. this review, we summarize discuss potential on counteracting aging-associated demyelination, which causes cognitive decline AD. We highlight need further basic clinical research investigations topic establish novel approaches healthy aging.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

231
NLRP3 inflammasome signalling in Alzheimer's disease DOI Creative Commons
Róisín M. McManus, Eicke Latz

Neuropharmacology, Journal Year: 2024, Volume and Issue: 252, P. 109941 - 109941

Published: March 31, 2024

Every year, 10 million people develop dementia, the most common of which is Alzheimer's disease (AD). To date, there no way to prevent cognitive decline and therapies are limited. This review provides a neuroimmunological perspective on progression AD, discusses immune-targeted that in preclinical clinical trials may impact development this disease. Specifically, we look role NLRP3 inflammasome, its triggers brain how activation can contribute dementia. We summarise range inhibitors targeting inflammasome downstream pathways under investigation, discuss future therapeutic perspectives for devastating condition.

Language: Английский

Citations

25
Targeting aging and age-related diseases with vaccines DOI
R. H. Wu, Fei Sun, Weiqi Zhang

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(4), P. 464 - 482

Published: April 15, 2024

Language: Английский

Citations

25
Inflammatory aspects of Alzheimer’s disease DOI
Pablo Botella Lucena, Michael T. Heneka

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Aug. 28, 2024

Language: Английский

Citations

25
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy DOI Creative Commons
Qiuyang Zheng, Xin Wang

Protein & Cell, Journal Year: 2024, Volume and Issue: unknown

Published: May 11, 2024

Abstract Alzheimer’s disease (AD), the leading cause of dementia, is characterized by accumulation amyloid plaques and neurofibrillary tangles in brain. This condition casts a significant shadow on global health due to its complex multifactorial nature. In addition genetic predispositions, development AD influenced myriad risk factors, including aging, systemic inflammation, chronic conditions, lifestyle, environmental exposures. Recent advancements understanding pathophysiology are paving way for enhanced diagnostic techniques, improved assessment, potentially effective prevention strategies. These discoveries crucial quest unravel complexities AD, offering beacon hope management treatment options millions affected this debilitating disease.

Language: Английский

Citations

24
Single-cell multiplex chromatin and RNA interactions in ageing human brain DOI Creative Commons
Xingzhao Wen, Zhifei Luo,

Wenxin Zhao

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8008), P. 648 - 656

Published: March 27, 2024

Abstract Dynamically organized chromatin complexes often involve multiplex interactions and sometimes chromatin-associated RNA 1–3 . Chromatin complex compositions change during cellular differentiation ageing, are expected to be highly heterogeneous among terminally differentiated single cells 4–7 Here we introduce the multinucleic acid interaction mapping in (MUSIC) technique for concurrent profiling of interactions, gene expression RNA–chromatin associations within individual nuclei. When applied 14 human frontal cortex samples from older donors, MUSIC delineated diverse cortical cell types states. We observed that nuclei exhibiting fewer short-range were correlated with both an ‘older’ transcriptomic signature Alzheimer’s disease pathology. Furthermore, type contacts between cis quantitative trait loci a promoter tends which these specifically affect their target gene. In addition, female exhibit XIST non-coding chromosome X, along spatial organizations X chromosomes. presents potent tool exploration architecture transcription at resolution tissues.

Language: Английский

Citations

23
Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice DOI Creative Commons
Andrew Octavian Sasmita, Constanze Depp,

T. I. Nazarenko

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1668 - 1674

Published: Aug. 5, 2024

Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant oligodendrocytes (OLs). By cell-type-specific deletion Bace1 a humanized knock-in AD model, APP

Language: Английский

Citations

23
Oligodendrocytes: Myelination, Plasticity, and Axonal Support DOI
Mikael Simons, Erin M. Gibson, Klaus‐Armin Nave

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(10), P. a041359 - a041359

Published: April 15, 2024

Mikael Simons1,2, Erin M. Gibson3 and Klaus-Armin Nave4 1Institute of Neuronal Cell Biology, Technical University Munich, Munich 80802, Germany 2German Center for Neurodegenerative Diseases, Cluster Systems Neurology (SyNergy), Institute Stroke Dementia Research, 81377, 3Department Psychiatry Behavioral Sciences, Stanford School Medicine, 94305, California, USA 4Department Neurogenetics, Max Planck Multidisciplinary Göttingen 37075, Correspondence: mikael.simons{at}dzne.de; egibson1{at}stanford.edu; nave{at}mpinat.mpg.de

Language: Английский

Citations

19
Neuroinflammation in Alzheimer disease DOI
Wiesje M. van der Flier, Wiesje M. van der Flier,

Frank Jessen

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Language: Английский

Citations

18
Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer’s disease DOI Creative Commons
Andrew Octavian Sasmita,

Erinne Cherisse Ong,

T. I. Nazarenko

et al.

Neuron, Journal Year: 2025, Volume and Issue: 113(6), P. 838 - 846.e4

Published: Jan. 20, 2025

In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether parental origin of transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance led 2-fold higher burden compared maternal inheritance, finding consistent across multiple colonies. This effect was not due gestation in or rearing by females. Immunoblotting suggested transgenic modulates protein expression, potentially genomic imprinting Thy1.2 promoter. Surprisingly, fewer than 20% studies report breeding schemes, suggesting this factor might confound previous findings. Our data highlight significant determinant mice and underscore importance reporting improve scientific rigor reproducibility research.

Language: Английский

Citations

4