Targeting the molecular web of Alzheimer’s disease: unveiling pathways for effective pharmacotherapy

The Egyptian Journal of Neurology Psychiatry and Neurosurgery, Год журнала: 2024, Номер 60(1)

Опубликована: Янв. 11, 2024

Abstract Introduction Alzheimer’s disease is a neurocognitive disorder that affects elderly people by slowly impaired cognition, dementia, and gets worse with age. It impacts the quality of life. Clinically, it distinguished transition from episodic memory to gradual reduction in cognitive ability leading dysfunction. Neurofibrillary tangles amyloid plaques are unique structures thought have role pathogenesis Alzheimer's disease. In this review, we focus our attention on risk factors, pathophysiology, etiology, epidemiology, stages, diagnosis, treatment, mechanisms, pathways, ongoing clinical trials data risks potentially associated development Short summary This review aims extrapolate information about Preliminary research was done selecting reviews PubMed, Elsevier, Google open-access publications using keywords like “Alzheimer, neurodegenerative, memory, β, mechanism action, pathways”. Conclusion Here show discussion interpretation several signaling pathways such as β plaque cleavage, Metal ion hypothesis, degradation, initiation amyloidogenic non-amyloidogenic pathway, oxidative stress Metabolic syndrome, insulin resistance tau phosphorylation apolipoprotein- cholesterol, neurofibrillary accumulation, which significant for better understanding progression. On studying trials, found current drugs being tested crenezumab, gantenerumab sodium oligonucleotide. Graphical

Язык: Английский

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The ROSMAP project: aging and neurodegenerative diseases through omic sciences

Frontiers in Neuroinformatics, Год журнала: 2024, Номер 18

Опубликована: Сен. 16, 2024

The Religious Order Study and Memory Aging Project (ROSMAP) is an initiative that integrates two longitudinal cohort studies, which have been collecting clinicopathological molecular data since the early 1990s. This extensive dataset includes a wide array of omic data, revealing complex interactions between levels in neurodegenerative diseases (ND) aging. Neurodegenerative are frequently associated with morbidity cognitive decline older adults. Omics research, conjunction clinical variables, crucial for advancing our understanding diagnosis treatment diseases. summary reviews omics research—encompassing genomics, transcriptomics, proteomics, metabolomics, epigenomics, multiomics—conducted through ROSMAP study. It highlights significant advancements mechanisms underlying diseases, particular focus on Alzheimer's disease.

Язык: Английский

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Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer’s disease

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 4, 2025

Abstract Background PSEN1, PSEN2, and APP mutations cause Alzheimer’s disease (AD) with an early age at onset (AAO) progressive cognitive decline. PSEN1 are more common generally have earlier AAO; however, certain a later AAO, similar to those observed in PSEN2 . Methods We examined whether endotypes exist across these AAO (~ 55 years) using hiPSC-derived neurons from familial (FAD) patients harboring A79V , N141I V717I mechanistically characterized by integrating RNA-seq ATAC-seq. Results identified endotypes, such as dedifferentiation, dysregulation of synaptic signaling, repression mitochondrial function metabolism, inflammation. ascertained the master transcriptional regulators associated including REST, ASCL1, ZIC family members (activation), NRF1 (repression). Conclusions FAD share regulatory changes within varying severity, resulting reversion less-differentiated state. The mechanisms described offer potential targets for therapeutic interventions.

Язык: Английский

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Exercise-Induced Modulation of Neuroinflammation in Models of Alzheimer’s Disease

Brain Plasticity, Год журнала: 2018, Номер 4(1), С. 81 - 94

Опубликована: Дек. 12, 2018

Alzheimer's disease (AD), a progressive, neurodegenerative condition characterised by accumulation of toxic βeta-amyloid (Aβ) plaques, is one the leading causes dementia globally. The cognitive impairment that hallmark AD may be caused inflammation in brain triggered and maintained presence Aβ protein, ultimately to neuronal dysfunction loss. Since there significant inflammatory component AD, it postulated anti-inflammatory strategies prophylactic or therapeutic benefit AD. One such strategy regular physical activity, which has been shown epidemiological studies protective against various forms including Exercise induces an environment peripheral organs also increases expression molecules within brain. Here we review evidence, mainly from animal models supporting hypothesis exercise can reduce slow cellular impairments associated with modulating neuroinflammation.

Язык: Английский

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Exploring the Role of PSEN Mutations in the Pathogenesis of Alzheimer’s Disease

Neurotoxicity Research, Год журнала: 2020, Номер 38(4), С. 833 - 849

Опубликована: Июнь 18, 2020

Язык: Английский

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