Immediate and deferred epigenomic signatures of in vivo neuronal activation in mouse hippocampus

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(10), P. 1718 - 1730

Published: Sept. 9, 2019

Language: Английский

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Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 30, 2023

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis poorly understood. The heritability estimate of MDD 30-40%, suggesting genetics alone do not account for most the risk major depression. Another factor known to associate with involves environmental stressors such as childhood adversity recent life stress. Recent studies have emerged show biological impact factors in other stress-related disorders mediated by variety epigenetic modifications. These modification alterations contribute abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission neuroglia dysfunction, which are involved pathophysiology MDD. Furthermore, marks been associated diagnosis treatment evaluation modifications holds promise further understanding heterogeneous etiology complex phenotypes MDD, may identify new therapeutic targets. Here, we review preclinical clinical findings, including DNA methylation, histone modification, noncoding RNA, RNA chromatin remodeling In addition, elaborate on contribution these mechanisms pathological trait variability depression discuss how can be exploited purposes.

Language: Английский

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Scrutinizing the epigenetics revolution

BioSocieties, Journal Year: 2014, Volume and Issue: 9(4), P. 431 - 456

Published: Aug. 4, 2014

Epigenetics is one of the most rapidly expanding fields in life sciences. Its rise frequently framed as a revolutionary turn that heralds new epoch both for gene-based epistemology and wider discourse on pervades knowledge-intensive societies molecular age. The fundamentals this revolution remain however to be scrutinized, indeed very contours what counts 'epigenetic' are often blurred. This reflected also mounting societal implications epigenetics, which vast expectations coexist with significant uncertainty about aspects science relevant politics or policy alike. therefore suitable time reflect directions social theory could productively take scrutiny revolution. Here we opportunity its scholarly normative dimension, is, proposing roadmap theorizing epigenetics does not shy away from, hopefully guides, framing socially outputs. To end, start an epistemological reappraisal epigenetic valorizes blurring meanings critical asset field privileged analytical entry point. We then propose three paths investigation. first looks at structuring elements controversies visions around epigenetics. second probes mutual constitution between reordering living phenomena settlements orient individual collective responsibilities. third highlights material import molecularization culture it mediates. suggest these complementary strands provide epistemically self-reflective framework advance study juncture nature nurture thus frontier studies

Language: Английский

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Mechanisms of Melatonin in Alleviating Alzheimer’s Disease

Current Neuropharmacology, Journal Year: 2017, Volume and Issue: 15(7)

Published: March 15, 2017

Alzheimer's disease (AD) is a chronic, progressive and prevalent neurodegenerative characterized by the loss of higher cognitive functions an associated memory. The thus far "incurable" stigma for AD prevails because variations in success rates different treatment protocols animal human studies. Among classical hypotheses explaining pathogenesis, amyloid hypothesis currently being targeted drug development. underlying concept to prevent formation these neurotoxic peptides which play central role pathology trigger multispectral cascade processes post-aggregation. This could possibly be achieved pharmacological inhibition β- or γ-secretase stimulating nonamyloidogenic α-secretase. Melatonin pineal hormone multifunctioning indoleamine. Production this amphiphilic molecule diminishes with advancing age decrease runs parallel progression itself explains potential benefits melatonin line development devastating consequences progression. Our recent studies have revealed novel mechanism stimulates processing inhibits amyloidogenic β-amyloid precursor protein (βAPP) α -secretases consequently down regulating both γ-secretases at transcriptional level. In review, we discuss evaluate neuroprotective including its cellular models clinical interventions patients, suggest that early detection, qualified anti-AD therapy. Keywords: disease, aging, amyloid-β peptide, melatonin, secretases, neuroprotection.

Language: Английский

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Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice

Brain, Journal Year: 2017, Volume and Issue: 140(12), P. 3252 - 3268

Published: Oct. 5, 2017

The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic that clusters glutamate receptors and is critical plasticity. PSD95 levels are diminished in ageing neurodegenerative disorders, including Alzheimer's disease Huntington's disease. epigenetic mechanisms (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, largely unknown, limiting the development targeted epigenome therapy. We analysed Dlg4/PSD95 landscape hippocampal tissue designed gene-targeting strategy: zinc finger DNA-binding domain was engineered fused to effector domains either repress (G9a, Suvdel76, SKD) activate (VP64) transcription, generating artificial factors editors (methylating H3K9). These epi-editors altered histone marks subsequently expression, which, importantly, impacted several neuron processes. Intriguingly, transduction factor PSD95-VP64 rescued memory deficits aged mice. Conclusively, this work validates as key player establishes editing potential therapy treat human neurological disorders.

Language: Английский

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