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Aims: Alzheimer's disease is considered one of the most prevalent neurodegenerative disorders and dementia is the core symptom of this disease. This study was aimed to test the bioactive compounds produced by endophytic fungus for the inhibition of acetylcholinesterase (AChE) activity and to identify the compound responsible for this activity. Methods and Results: Endophytic fungi were isolated from the medicinal plant Tinospora cordifolia and screened for AChE inhibition and antioxidant activity. The extract of one of the isolates Nigrospora oryzae (GL15) showed maximum AChE inhibition as well as antioxidant activity. The compound responsible for AChE inhibition (fraction 3) was identified as quercetin based on UV, FTIR spectra, HPLC and ESI‐MS analyses. Furthermore, the identification of quercetin in the extract of fraction 3 was confirmed by 1H NMR analysis. This extract showed anti‐dementia‐like activity in scopolamine (SCO) model. The minimal effective dose of the extract of fraction 3 modulated the SCO‐provoked cognitive deficits such as impairments in spatial recognition memory and latency period in Y‐maze test and passive avoidance test, respectively. The SCO‐induced modulation in cholinergic pathway was ameliorated by the extract of N. oryzae in hippocampus, resulting in decrease in AChE activity and restoration of cytoarchitecture of hippocampus. Conclusions: The bioactive compound quercetin produced by N. oryzae may cure the learning and memory shortfalls via AChE‐mediated mechanism in experimental mice. Significance and Impact of the Study: The endophytic fungus N. oryzae serves as a potential source for the bioactive compound quercetin, which plays an important role in the management of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) remains one of the most formidable neurological disorders, affecting millions globally. This review provides a holistic overview of the therapeutic strategies, both conventional and novel, aimed at mitigating the impact of AD. Initially, we delve into the conventional approach, emphasizing the role of Acetylcholinesterase (AChE) inhibition, which has been a cornerstone in AD management. As our understanding of AD evolves, several novel potential approaches emerge. We discuss the promising roles of Butyrylcholinesterase (BChE) inhibition, Tau Protein inhibitors, COX-2 inhibition, PPAR-γ agonism, and FAHH inhibition, among others. The potential of the endocannabinoids (eCB) system, cholesterol-lowering drugs, metal chelators, and MMPs inhibitors are also explored, culminating in the exploration of the pivotal role of microRNA in AD progression. Parallel to these therapeutic insights, we shed light on the novel tools and methodologies revolutionizing AD research. From the quantitative analysis of gene expression by qRTPCR to the evaluation of mitochondrial function using induced pluripotent stem cells (iPSCs), the advances in diagnostic and research tools offer renewed hope. Moreover, we explore the current landscape of clinical trials, highlighting the leading drug interventions and their respective stages of development. This comprehensive review concludes with a look into the future perspectives, capturing the potential breakthroughs and innovations on the horizon. Through a synthesis of current knowledge and emerging research, this article aims to provide a consolidated resource for clinicians, researchers, and academicians in the realm of Alzheimer's disease. [Display omitted] • Unveils novel AD therapeutic strategies. • Detailed specific mitochondrial changes in AD. • Analyzed AD's mitochondrial dysfunction. • Explored iPSCs for AD mitochondrial insights. • Evaluates animal models' relevance to AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Offered detailed examination of various neurotransmitter pathways implicated in Alzheimer's Disease, including cholinergic, glutamatergic, and GABAergic systems. • Explored the dual role of microglia in Alzheimer's progression, highlighting their neuroprotective and neuroinflammatory actions and their therapeutic potential. • Discussed the emerging significance of Alpha-7 Nicotinic Acetylcholine Receptors in AD, emphasizing their role in cognitive functions and potential as therapeutic targets. • Critically assessed the existing therapeutic strategies for AD, including NMDA inhibitors and anti-amyloid therapies, and explores promising future interventions. • Addressed the impact of AD beyond biological aspects, considering emotional, psychological, and social factors, and emphasizing the importance of holistic patient care. Alzheimer's Disease (AD) represents a complex interplay of neurological pathways and molecular mechanisms, with significant impacts on patients' lives. This review synthesizes the latest developments in AD research, focusing on both the scientific advancements and their clinical implications. We examine the role of microglia in AD, highlighting their contribution to the disease's inflammatory aspects. The cholinergic hypothesis, a cornerstone of AD research, is re-evaluated, including the role of Alpha-7 Nicotinic Acetylcholine Receptors in disease progression. This review places particular emphasis on the neurotransmission systems, exploring the therapeutic potential of GABAergic neurotransmitters and the role of NMDA inhibitors in the context of glutamatergic neurotransmission. By analyzing the interactions and implications of neurotransmitter pathways in AD, we aim to shed light on emerging therapeutic strategies. In addition to molecular insights, the review addresses the clinical and personal aspects of AD, underscoring the need for patient-centered approaches in treatment and care. The final section looks at the future directions of AD research and treatment, discussing the integration of scientific innovation with patient care. This review aims to provide a comprehensive update on AD, merging scientific insights with practical considerations, suitable for both specialists and those new to the field. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aβ) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aβ, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease. • miRNAs regulate key AD pathologies. • Aβ, tau impact on neuronal health. • Novel miRNA-based therapies explored. • Challenges in miRNA therapy delivery. • Future: personalized AD treatments. [ABSTRACT FROM AUTHOR]