Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 252 - 252

Published: Feb. 27, 2025

Neurological disorders are defined by a deterioration or disruption of the nervous system’s structure and function. These diseases, which include multiple sclerosis, Alzheimer’s disease, Parkinson’s Huntington’s schizophrenia, caused intricate pathological processes that excitotoxicity, neuroinflammation, oxidative stress, genetic mutations, compromised neurotrophic signaling. Although current pharmaceutical treatments relieve symptoms, their long-term efficacy is limited due to adverse side effects weak neuroprotective properties. However, when combined with other drugs adjunct therapy, they may offer additional benefits improve treatment outcomes. Phytochemicals have emerged as attractive therapeutic agents ability regulate essential pathways, especially brain-derived factor (BDNF) signaling cascade. BDNF an important target for neurodegenerative disease (ND) since it regulates neuronal survival, synaptic plasticity, neurogenesis, neuroprotection. This review emphasizes molecular pathways through various phytochemicals—such flavonoids, terpenoids, alkaloids, phenolic compounds—stimulate expression modulate its downstream including GSK-3β, MAPK/ERK, PI3K/Akt/mTOR, CREB, Wnt/β-catenin. paper also highlights how phytochemical combinations interact enhance activity, offering new options ND treatment. Despite potential neuroprotection, phytochemicals face challenges related pharmacokinetics, blood–brain barrier (BBB) permeability, absorption, highlighting need further research into combination therapies improved formulations. Clinical assessment mechanistic understanding BDNF-targeted phytotherapy should be main goals future studies. The natural compounds in regulating highlighted this review, providing viable approach prevention NDs.

Language: Английский

Fused and Substituted Piperazines as Anticancer Agents: A Review

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(3)

Published: March 1, 2025

Cancer is an abnormal and uncontrolled proliferation of normal cells. The availability safer anticancer drugs with exceptional selectivity for healthy cells great efficacy against various cancer forms continues to be a significant obstacle. piperazine moiety used as the building block several molecules reported have ability inhibit cell cycle (G1/S phase), angiogenesis, interact DNA. Piperazine also has flexible binding feature that allows it variety biological targets, which makes effective cancers. As there continuous need obtain drug improved fewer side effects, derivatives attract attention researchers. This review highlights recently methods synthesis fused/substituted piperazines, structure-activity relationship, interactions targets/receptors agents. Thus, presented will help medicinal chemists in designing piperazines.

Language: Английский

Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3252 - 3252

Published: April 1, 2025

Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation and immune cell infiltration, is linked to plaque formation cardiovascular events. While traditionally associated with metabolism endothelial dysfunction, recent research highlights the roles of autophagy clonal hematopoiesis (CH) in its pathogenesis. Autophagy, cellular process crucial for degrading damaged components, regulates macrophage homeostasis inflammation, both which are pivotal atherosclerosis. In macrophages, influences metabolism, cytokine regulation, oxidative stress, helping prevent instability. Defective exacerbates impairs cholesterol efflux, accelerates progression. Additionally, autophagic processes cells smooth muscle further contribute atherosclerotic pathology. Recent studies also emphasize interplay between CH, wherein somatic mutations genes like TET2, JAK2, DNMT3A drive expansion enhance responses plaques. These modify function, intensifying environment accelerating Chaperone-mediated (CMA), selective form autophagy, plays critical role regulating inflammation pro-inflammatory cytokines oxidized low-density lipoprotein (ox-LDL). Impaired CMA activity leads these substrates, activating NLRP3 inflammasome worsening inflammation. Preclinical suggest that pharmacologically may mitigate atherosclerosis animal models, reduced instability increases This review importance regulation focusing on formation, contributions CH. Building upon current advances, we propose hypothesis programmed death, intrinsic axis modulates fundamental functions playing complex development Understanding mechanisms offers potential therapeutic strategies targeting reduce burden disease.

Language: Английский