Alzheimer’s disease (AD) remains one of the most debilitating neurodegenerative disorders, with its pathological hallmark being progressive cognitive decline and memory loss. Recent research has illuminated the crucial role of the brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS), highlighting its impact on neurogenesis, synaptic plasticity, and neuronal survival. Dysregulation of the BDNF signaling axis, particularly the imbalance between its precursor form and mature BDNF, is strongly implicated in the pathophysiology of AD. This review explores the molecular mechanisms through which BDNF modulates AD neuropathology and presents novel therapeutic strategies to activate BDNF signaling. We focus on the potential of BDNF activators, such as TrkB agonists and mimetic molecules, to restore synaptic function and ameliorate cognitive deficits in AD. Furthermore, we examine the challenges in translating these findings into clinical practice, including issues with blood–brain barrier penetration and the need for precise receptor targeting. The review emphasizes the therapeutic potential of repurposed drugs, including statins and metformin, in enhancing BDNF signaling and offers new insights into the future of AD treatment. Ultimately, this work provides a compelling argument for BDNF-based therapies as a promising avenue for mitigating the cognitive decline associated with Alzheimer’s disease, signaling a hopeful direction for future research and clinical trials.

Tirzepatide (TRZ) is a dual agonist of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptors that were recently approved for the treatment of type 2 diabetes (T2D) and obesity. Of note is that T2D and obesity, by inducing peripheral low-grade inflammation and oxidative stress, provoke the development of central neuroinflammation and oxidative stress. Together, T2D and obesity are regarded as potential risk factors implicated in the development and progression of Alzheimer’s disease (AD), which is the most common neurodegenerative disease and represents the most typical cause of dementia. Hence, targeting low-grade inflammation and oxidative stress in T2D and obesity by TRZ may reduce AD neuropathology. In addition, TRZ can inhibit the production of amyloid beta (Aβ) and associated neuroinflammation, oxidative stress, and neuronal apoptosis. However, the underlying neuroprotective mechanism of TRZ against AD is not entirely explained. Consequently, this mini-review aims to discuss the possible molecular mechanism of TRZ in AD.

Metformin is an anti-diabetic drug used in the management of type 2 diabetes (T2D). Metformin has different pleiotropic effects, such as anti-inflammatory, antioxidant, antithrombotic, and vasculoprotective. Metformin has neuroprotective effects against neurodegenerative diseases and ischemic stroke. Conversely, metformin may exacerbate the pathogenesis of ischemic stroke. This controversial point may be related to the impact of metformin on the different signaling pathways, such as AMP-activated protein kinase (AMPK) and growth differentiation factor 15 (GDF-15). Many studies have reported the effect of metformin on ischemic stroke, with AMPK signaling only. However, little has been explored about the impact of metformin on the GDF-15 signaling in ischemic stroke. Accordingly, this review aims to discuss the role of metformin in the neuropathology of ischemic stroke regarding the AMPK and GDF-15 signaling pathways.

The brain undergoes profound molecular and structural changes during the aging process, resulting in the development of neurodegeneration, cognitive impairment, and increased vulnerability to chronic diseases. At the cellular level, brain aging is characterized by oxidative damage, genomic instability, and chronic low-grade inflammation known as inflammaging. Central to this process is Sirtuin 1 (SIRT1), a NAD ⁺ -dependent class III histone deacetylase, known for its regulatory role in chromatin remodeling, oxidative stress responses, mitochondrial biogenesis, and neuroplasticity. Recent research has identified SIRT1 as a molecular target capable of reversing or attenuating several hallmarks of aging, particularly within the central nervous system (CNS). This narrative review critically evaluates the emerging evidence surrounding the geroprotective effects of SIRT1 activators, which exert dual actions, senomorphic and senolytic, via modulation of signaling pathways, thereby reducing neuronal senescence, enhancing autophagy, and mitigating inflammatory responses. The discussion also addresses the region-specific role of SIRT1 across the brain, particularly in the hippocampus and hypothalamus, which are essential for memory, energy homeostasis, and resilience to stress. Additionally, this review explores how SIRT1 depletion during aging contributes to the development of synaptic dysfunction, impaired cognitive function, and susceptibility to neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The therapeutic potential of SIRT1 activators is supported by preclinical and early clinical studies, suggesting their value in preventing or delaying brain aging. Thus, SIRT1 could be a promising pharmacological target for age-associated brain disorders, warranting more robust translational studies to validate these findings in humans.

Non-communicable diseases, such as diabetes, cancer, as well as cardiovascular, metabolic, and central nervous system disorders stand for significant global health burden. Statins, as HMG-CoA reductase inhibitors, have emerged as a basis in the management of hypercholesterolemia and the prevention of cardiovascular disorders. In this review, we summarize the role of statins in a variety of pathologies, ranging from their well-recognized effects in cardiovascular disorders, to the newly revealed favorable effects in cancer, eye, autoimmune, kidney, gastrointestinal, bone, and autoimmune disorders. Additionally, the current review explores insights into the potential role of natural products as HMG-CoA reductase inhibitors. Future research should focus on the synergistic effects of natural therapies with synthetic statins to improve health outcomes in populations burdened by non-communicable diseases.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver–gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood–brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid–based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.