Targeting Abnormal Tau Phosphorylation for Alzheimer’s Therapeutics DOI
Aditya Singh, Valeed Ahmad Ansari, Tarique Mahmood

и другие.

Hormone and Metabolic Research, Год журнала: 2024, Номер 56(07), С. 482 - 488

Опубликована: Фев. 13, 2024

Abstract Alzheimer’s disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: β-amyloid (Aβ) tau protein. While amyloid cascade theory has long dominated research, recent developments have ignited debates about its centrality. Aβ plaques NFTs are hallmark pathologies AD. Aducanumab lecanemab, monoclonal antibodies targeting Aβ, been approved, albeit amidst controversy, raising questions therapeutic efficacy of Aβ-focused interventions. On other hand, tau, specifically hyperphosphorylation, disrupts microtubule stability contributes to neuronal dysfunction. Various post-translational modifications drive aggregation into NFTs. Emerging treatments such as GSK-3β CDK5 inhibitors, shown promise preclinical clinical studies. Restoring equilibrium protein kinases phosphatases, notably phosphatase-2A (PP2A), promising avenue for therapy, primarily regulated phosphorylation state. Activation tau-specific phosphatases offers potential mitigating pathology. The evolving landscape drug development emphasizes tau-centric therapies reevaluation hypothesis. Additionally, exploring role neuroinflammation interaction with pathology present research directions.

Язык: Английский

Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects DOI Creative Commons
Bin Tong,

Yaoqi Ba,

Zhengyang Li

и другие.

Neurobiology of Disease, Год журнала: 2024, Номер 196, С. 106505 - 106505

Опубликована: Апрель 19, 2024

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features AD memory decline cognitive dysfunction, while PD mainly manifests as motor dysfunction such limb tremors, muscle rigidity abnormalities, slow gait. Abnormalities in cholesterol, sphingolipid, glycerophospholipid metabolism have been demonstrated to directly exacerbate progression by stimulating Aβ deposition tau protein tangles. Indirectly, abnormal lipids can increase burden on brain vasculature, induce insulin resistance, affect structure neuronal cell membranes. Abnormal lipid leads through inducing accumulation α-syn, mitochondria endoplasmic reticulum, ferroptosis. Great progress has made targeting abnormalities for treatment recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, monoclonal antibodies apolipoprotein E (ApoE). This review comprehensively summarizes involvement dysregulated pathogenesis PD, application Lipid Monitoring, emerging regulatory drug targets. A better understanding lipidological bases may pave way developing effective prevention methods neurodegenerative disorders.

Язык: Английский

Процитировано

17
Cyclin-dependent protein kinases and cell cycle regulation in biology and disease DOI Creative Commons
Ilenia Pellarin, Alessandra Dall’Acqua, Andrea Favero

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 12, 2025

Abstract Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified as kinases able drive division. In reality, human genome contains 20 different CDKs, which can be divided in at least three sub-family with functions, mechanisms regulation, expression patterns and subcellular localization. Most these play fundamental roles normal physiology eucaryotic cells; therefore, their deregulation is associated onset and/or progression multiple disease including but not limited neoplastic neurodegenerative conditions. Here, we describe functions categorized into main functional groups they classified, highlighting most relevant pathways that functions. We then discuss potential CDKs pathologies, a particular focus on cancer, have extensively studied explored therapeutic targets. Finally, how inhibitors become standard therapies selected cancers propose novel ways investigation export targeting from cancer other chronic diseases. hope effort made collecting all available information both prominent lesser-known CDK family members will help identify develop areas research improve lives patients affected by debilitating

Язык: Английский

Процитировано

9
Lipidome disruption in Alzheimer’s disease brain: detection, pathological mechanisms, and therapeutic implications DOI Creative Commons
Sijia He, Ziying Xu, Xianlin Han

и другие.

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 27, 2025

Alzheimer's disease (AD) is among the most devastating neurodegenerative disorders with limited treatment options. Emerging evidence points to involvement of lipid dysregulation in development AD. Nevertheless, precise lipidomic landscape and mechanistic roles lipids pathology remain poorly understood. This review aims highlight significance lipidomics lipid-targeting approaches diagnosis We summarized connection between human brain AD at both genetic species levels. briefly introduced technologies discussed potential challenges areas future advancements field for research. To elucidate central role converging multiple pathological aspects AD, we reviewed current knowledge on interplay major features, including amyloid beta, tau, neuroinflammation. Finally, assessed progresses obstacles lipid-based therapeutics proposed strategies leveraging

Язык: Английский

Процитировано

2
Current Advances in the Therapeutic Potential of Scutellarin: Novel Applications, Mechanisms, and Future Challenges. DOI Creative Commons
Great Iruoghene Edo, Alice Njolke Mafe, Patrick Othuke Akpoghelie

и другие.

Phytomedicine Plus, Год журнала: 2025, Номер unknown, С. 100754 - 100754

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies DOI Creative Commons
Sagar Gaikwad, Sudipta Senapati, Md. Anzarul Haque

и другие.

Alzheimer s & Dementia, Год журнала: 2023, Номер 20(1), С. 709 - 727

Опубликована: Окт. 9, 2023

Abstract Aging, tau pathology, and chronic inflammation in the brain play crucial roles synaptic loss, neurodegeneration, cognitive decline tauopathies, including Alzheimer's disease. Senescent cells accumulate aging brain, accelerate process, promote tauopathy progression through their abnormal inflammatory secretome known as senescence‐associated secretory phenotype (SASP). Tau oligomers (TauO)—the most neurotoxic species—are to induce senescence SASP, which subsequently neuropathology, inflammation, oxidative stress, dysfunction, neuronal death, dysfunction. TauO, are associated with heterogeneity decline. However, underlying mechanisms driving disease remain largely unknown, impeding development of therapies for tauopathies. Based on clinical preclinical evidence, this review highlights critical role TauO neurodegeneration. We discuss key knowledge gaps potential strategies targeting treat Highlights Senescence, oligomeric (TauO), process contributing highlight target tauopathies while addressing gaps.

Язык: Английский

Процитировано

31
Navigating the dementia landscape: Biomarkers and emerging therapies DOI

Shubhrat Maheshwari,

Aditya Singh, Valeed Ahmad Ansari

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 94, С. 102193 - 102193

Опубликована: Янв. 10, 2024

Язык: Английский

Процитировано

14
A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau DOI Creative Commons

Zhouquan Jiang,

Jing Wang,

Yongpeng Qin

и другие.

Alzheimer s Research & Therapy, Год журнала: 2024, Номер 16(1)

Опубликована: Янв. 27, 2024

Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities humans, making them ideal model animals for investigating pathogenesis AD potential therapies. However, use NHPs in research has been hindered by paucity monkey models due to their long generation time, ethical considerations, technical challenges genetically modifying monkeys. Methods Here, we developed an AD-like NHP overexpressing human tau bilateral hippocampi adult rhesus macaque We evaluated pathological features these monkeys immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), behavioural tests. Results demonstrated that after hippocampal overexpression protein, displayed multiple AD, including 3-repeat (3R)/4-repeat (4R) accumulation, hyperphosphorylation, propagation, neuronal loss, atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, cognitive decline. More interestingly, accumulation both 3R 4R specific but not found rodents. Conclusions This work establishes a tau-induced many key AD. In addition, our may potentially become adopted researchers worldwide since it can be generated within 2 ~ 3 months through single injection AAVs into brains. Hence, facilitate mechanistic studies therapeutic treatments

Язык: Английский

Процитировано

9
Loss of TMEM106B exacerbates Tau pathology and neurodegeneration in PS19 mice DOI
Tuancheng Feng, Huan Du,

Cha Yang

и другие.

Acta Neuropathologica, Год журнала: 2024, Номер 147(1)

Опубликована: Март 25, 2024

Язык: Английский

Процитировано

9
Gut instincts: Unveiling the connection between gut microbiota and Alzheimer's disease DOI

Vasu Peddinti,

Manoj Mohan Avaghade,

Sunil Suthar

и другие.

Clinical Nutrition ESPEN, Год журнала: 2024, Номер 60, С. 266 - 280

Опубликована: Фев. 19, 2024

Язык: Английский

Процитировано

8
The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings DOI Creative Commons
Jin Yang, Junyi Liang,

Niyuan Hu

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Окт. 1, 2024

Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, critical pathological feature of AD. Understanding role this process essential for uncovering new therapeutic avenues gaining deeper insights into AD pathogenesis.

Язык: Английский

Процитировано

8