Distinguishing features of depression in dementia from primary psychiatric disease

Discover Mental Health, Год журнала: 2024, Номер 4(1)

Опубликована: Янв. 4, 2024

Abstract Depression is a common and devastating neuropsychiatric symptom in the elderly patients with dementia. In particular, nearly 80% of Alzheimer’s Disease dementia experience depression during disease development progression. However, it unknown whether shares same molecular mechanisms as presenting primary psychiatric or occurs persists through alternative mechanisms. this review, we discuss how clinical presentation treatment differ between disease, focus on major depressive disorder. Then, hypothesize several that may be unique to such neuropathological changes, inflammation, vascular events. Finally, existing issues future directions for investigation

Язык: Английский

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Molecular switch of the dendrite-to-spine transport of TDP-43/FMRP-bound neuronal mRNAs and its impairment in ASD

Cellular & Molecular Biology Letters, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 15, 2025

Abstract Background Regulation of messenger RNA (mRNA) transport and translation in neurons is essential for dendritic plasticity learning/memory development. The trafficking mRNAs along the hippocampal neuron dendrites remains translationally silent until they are selectively transported into spines upon glutamate-induced receptor activation. However, molecular mechanism(s) behind spine entry under metabotropic glutamate (mGluR)-mediated neuroactivation long-term depression (LTD) as well fate these inside still elusive. Method Different imaging techniques, e.g., immunoprecipitation (IP), RNA-IP, Immunofluorescence (IF)/fluorescence situ hybridization (FISH), live cell imaging, tracking using beacon, mouse model study used to elucidate a novel mechanism regulating mammalian neurons. Results We demonstrate here that brief mGluR1 activation-mediated dephosphorylation pFMRP (S499) results dissociation FMRP from TDP-43 handover TDP-43/ Rac1 mRNA complex track on microtubules myosin V actin filaments. thus enters translational reactivation increases mature density. In contrast, during mGluR1-mediated neuronal LTD, phosphorylated complex, being associated with kinesin 1-FMRP/cortactin/drebrin, owing Ca 2+ -dependent microtubule invasion spines, but without reactivation. VPA-ASD model, this regulation become anomalous. Conclusions This study, first time, highlights importance posttranslational modification RBPs, such neurodevelopmental disease-related protein FMRP, switch dendrite-to-spine specific neurotransmissions. misregulation could contribute pathogenesis FMRP-related neurodisorders including autism spectrum disorder (ASD). It also indicate connection between ASD neurodegenerative opens up new perspective research proteinopathy among patients ASD.

Язык: Английский

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Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders

Microbes and Infection, Год журнала: 2025, Номер unknown, С. 105479 - 105479

Опубликована: Фев. 1, 2025

Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8% of human increasingly recognized to be involved in etiology pathophysiology numerous brain disorders. In this narrative review, we summarize existing evidence linking abnormal HERV expression neurodevelopmental psychosis-related disorders discuss how these may contribute heterogeneity clinical outcomes. We also review findings suggesting aberrant late-onset cognitive with neurodegenerative components, such as Alzheimer's disease (AD) other forms dementia. conclude implicating neurodevelopmental, psychotic, is manifold stems from diverse research fields, including post-mortem studies, serological investigations, gene analyses, trials HERV-specific pharmacological compounds. The recent establishment use animal models offer a complementary experimental platform will help establish causal relationships identify specific pathways affected by expression. Yet, significant gaps persist understanding role HERVs disorders, particularly concerning specificity stability conditions. Addressing unresolved questions appears crucial for optimizing potential benefits therapeutic interventions aimed at targeting across broad spectrum HERV-associated CNS

Язык: Английский

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The potential of multimolecular G-quadruplex structures for targeted treatment of Amyotrophic Lateral Sclerosis

Expert Opinion on Therapeutic Targets, Год журнала: 2025, Номер unknown, С. 1 - 4

Опубликована: Фев. 4, 2025

Язык: Английский

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TDP-43 as a potential retinal biomarker for neurodegenerative diseases

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 12, 2025

TDP-43 proteinopathies are a spectrum of neurodegenerative diseases (NDDs) characterized by the pathological cytoplasmic aggregation protein. These include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and others. in eye shows promise as biomarker for these NDDs. Several studies have identified inclusions retinal layers donors with ALS, FTLD, AD, CTE, other conditions using immunohistochemistry. Our findings suggest that aggregates human retina most prevalent FTLD-TDP, suggesting may provide reliable context studying potential biomarker. Animal model been pivotal exploring TDP-43’s roles retina, including its nuclear localization, RNA binding properties, interactions proteins. Despite advances, more research is needed to develop therapeutic strategies. A major limitation autopsy lack corresponding brain pathology assessments confirm proteinopathy diagnosis staging. Other limitations small sample sizes, antemortem clinical histories, limited comparisons across multiple Future directions NDDs tracers, hyperspectral imaging, oculomics, machine learning development.

Язык: Английский

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