A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex DOI Creative Commons
Hankui Liu,

Honglin Hao,

Hui You

et al.

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(10), P. 1489 - 1501

Published: June 13, 2024

Abstract This study aimed to identify possible pathogenic genes in a 90-member family with rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known disease. We performed physical and neurological examinations International Rating Scales assess signs ataxia, Parkinsonism, cognitive function, as well brain magnetic resonance imaging scans seven sequences. searched for co-segregations abnormal repeat-expansion loci, variants spinocerebellar ataxia-related genes, novel mutations via whole-genome sequencing linkage analysis. A co-segregating missense mutation CARS gene was validated Sanger aminoacylation activity mutant measured spectrophotometric assay. pedigree presented late-onset core characteristics including cerebellar pyramidal all nine affected members. Brain showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF bilateral basal ganglia dentate nucleus, hypo-intensities nuclei, ganglia, mesencephalic red substantia nigra, suggested neurodegeneration. Whole-genome identified heterozygous (E795V) gene, meanwhile, exhibited none repeat-expansions or point genes. Remarkably, this causes 20% decrease charge tRNA Cys L-cysteine protein synthesis compared that wild type. All members carrying had same clinical manifestations neuropathological changes Parkinsonism spinocerebellar-ataxia. These findings pathogenesis Parkinsonism-spinocerebellar ataxia provide insights into its genetic architecture.

Language: Английский

Circadian disruption and human health DOI Open Access
Anna Fishbein, Kristen L. Knutson, Phyllis C. Zee

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes individual population levels. Evidence points a bidirectional relationship, in that circadian increases disease severity many diseases disrupt rhythms. Importantly, increase the risk for expression development of neurologic, psychiatric, cardiometabolic, immune disorders. Thus, harnessing rich findings from preclinical translational research biology enhance via circadian-based approaches represents unique opportunity personalized/precision medicine overall societal well-being. In this Review, we discuss implications human using bench-to-bedside approach. science applied clinical population-based Given broad regulation health, Review focuses its discussion on selected examples metabolic, cardiovascular, allergic, immunologic disorders highlight interrelatedness between potential interventions, such as bright light therapy exogenous melatonin, well chronotherapy improve and/or modify outcomes.

Language: Английский

Citations

232
Circadian disruption and sleep disorders in neurodegeneration DOI Creative Commons

Yun Shen,

Qian‐Kun Lv,

Wei-Ye Xie

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 13, 2023

Abstract Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions diseases. Circadian disruption disorders aggravate neurodegeneration in turn disrupt sleep. Importantly, various increase the risk Thus, harnessing biology findings from preclinical translational research is importance for reducing improving symptoms quality life individuals with via approaches that normalize context precision medicine. In this review, we discuss implications by summarizing both human animal studies, focusing on links prevalent forms neurodegeneration. These provide valuable insights into pathogenesis suggest promising role circadian-based interventions.

Language: Английский

Citations

65
NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson’s Disease DOI Creative Commons
Qiu-Qin Han, Weidong Le

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 39(5), P. 832 - 844

Published: Feb. 9, 2023

Abstract Parkinson’s disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in substantia nigra and formation Lewy bodies, which are mainly composed alpha-synuclein fibrils. Alpha-synuclein plays vital role neuroinflammation mediated nucleotide-binding oligomerization domain-, leucine-rich repeat-, pyrin domain-containing protein 3 (NLRP3) inflammasome PD. A better understanding NLRP3 inflammasome-mediated related mitochondrial impairment during PD progression may facilitate development promising therapies for This review focuses on molecular mechanisms underlying activation, comprising priming complex assembly, as well its subsequent inflammatory effects neurodegeneration In addition, therapeutic strategies targeting treatment discussed, including inhibitors pathways, mitochondria-focused treatments, microRNAs, other compounds.

Language: Английский

Citations

38
Assessment of stigma among patients living with Parkinson’s disease: an exploratory study DOI
Yue Huang,

Qing Fu,

De-feng Liu

et al.

Acta Neurologica Belgica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

1
Targeting the blood–brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays DOI Creative Commons
Yanping Wang, Weihong Du,

Xiaoyan Hu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(12), P. 4667 - 4687

Published: Aug. 14, 2023

The blood–brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity accelerated aging population. Importantly, also known to induce generation toxic metabolites pro-inflammatory cytokines, resulting BBB integrity. Collectively, this provides new perspective for exploring relationship among rhythms, microbes, diseases. In review, we focus on recent advances interplay between rhythm disturbances dysbiosis, their potential roles that occurs AAND. Based existing literature, discuss propose mechanisms underlying damage induced by dysregulated microbiota, which would serve as basis developing interventions protect population through targeting exploiting its links treating

Language: Английский

Citations

22
Relationship Between Short-chain Fatty Acids and Parkinson’s Disease: A Review from Pathology to Clinic DOI Creative Commons

Wen-Xiang Duan,

Fen Wang, Junyi Liu

et al.

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(4), P. 500 - 516

Published: Sept. 27, 2023

Parkinson's disease (PD) is a complicated neurodegenerative disease, characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies and neurites, massive loss midbrain dopamine neurons. Increasing evidence suggests that gut microbiota microbial metabolites are involved development PD. Among these, short-chain fatty acids (SCFAs), most abundant metabolites, have been proven to play key role brain-gut communication. In this review, we analyze SCFAs pathology PD from multiple dimensions summarize alterations patients as well their correlation with motor non-motor symptoms. Future research should focus on further elucidating neuroinflammation, developing novel strategies employing derivatives treat

Language: Английский

Citations

22
Loss of DJ-1 function contributes to Parkinson’s disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation DOI
Lele Liu, Yu Han, Zijia Zhang

et al.

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(10), P. 1948 - 1961

Published: May 25, 2023

Language: Английский

Citations

17
Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways DOI Creative Commons
Kenneth Maiese

Biomolecules, Journal Year: 2021, Volume and Issue: 11(7), P. 1002 - 1002

Published: July 9, 2021

Neurodegenerative disorders affect fifteen percent of the world's population and pose a significant financial burden to all nations. Cognitive impairment is seventh leading cause death throughout globe. Given enormous challenges treat cognitive disorders, such as Alzheimer's disease, inability markedly limit disease progression, circadian clock gene pathways offer an exciting strategy address loss. Alterations in genes can result age-related motor deficits, treatment regimens with neurodegenerative lead onset progression dementia. Interestingly, hold intricate relationship autophagy, mechanistic target rapamycin (mTOR), silent mating type information regulation 2 homolog 1

Language: Английский

Citations

37
Spatially resolved multiomics on the neuronal effects induced by spaceflight in mice DOI Creative Commons
Yuvarani Masarapu, Egle Cekanaviciute, Žaneta Andrusivová

et al.

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

Published: June 11, 2024

Abstract Impairment of the central nervous system (CNS) poses a significant health risk for astronauts during long-duration space missions. In this study, we employed an innovative approach by integrating single-cell multiomics (transcriptomics and chromatin accessibility) with spatial transcriptomics to elucidate impact spaceflight on mouse brain in female mice. Our comparative analysis between ground control spaceflight-exposed animals revealed alterations essential processes including neurogenesis, synaptogenesis synaptic transmission, particularly affecting cortex, hippocampus, striatum neuroendocrine structures. Additionally, observed astrocyte activation signs immune dysfunction. At pathway level, some spaceflight-induced changes exhibit similarities neurodegenerative disorders, marked oxidative stress protein misfolding. integrated serves as stepping stone towards understanding CNS impairments at level individual regions cell types, provides basis comparison future studies. For broader scientific impact, all datasets from study are available through interactive data portal, well National Aeronautics Space Administration (NASA) Open Science Data Repository (OSDR).

Language: Английский

Citations

5
Deciphering clock genes as emerging targets against aging DOI
Yanli Zhu,

Yanqing Liu,

Germaine Escames

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 81, P. 101725 - 101725

Published: Aug. 25, 2022

Language: Английский

Citations

21