Molecular Neurobiology最新文献

{"title":"Decoding Alzheimer's Disease: Single-Cell Sequencing Uncovers Brain Cell Heterogeneity and Pathogenesis.","authors":"Ya-Nan Ma, Ying Xia, Kenji Karako, Peipei Song, Wei Tang, Xiqi Hu","doi":"10.1007/s12035-025-04997-0","DOIUrl":"10.1007/s12035-025-04997-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by progressive cognitive decline and diverse neuropathological features. Recent advances in single-cell sequencing technologies have provided unprecedented insights into the cellular and molecular heterogeneity of the AD brain. This review systematically summarizes the applications of single-cell transcriptomic and epigenomic approaches in AD research, with a focus on the characterization of cell type- and subtype-specific transcriptomic alterations. This review highlights key discoveries related to selectively vulnerable neuronal and glial subpopulations, as well as transcriptional dysregulation associated with genetic risk loci such as APOE and TREM2. This review also discusses how the integration of single-cell RNA sequencing (scRNA-seq), assays for transposase-accessible chromatin using sequencing (ATAC-seq), and spatial transcriptomics elucidates disease trajectories and cellular communication networks across pathological stages. These insights not only enhance the understanding of the pathogenesis of AD but also pave the way for precision medicine through the identification of novel therapeutic targets and biomarkers.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14459-14473"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Central Role of Actin in Creutzfeldt-Jakob Disease: Unlocking Therapeutic Pathways.","authors":"Liliana Bastar-Juarez, Ximena Castillo-Estrada, Daniela Margarit-Mendez, Paola Coca-Gutierrez","doi":"10.1007/s12035-025-05112-z","DOIUrl":"10.1007/s12035-025-05112-z","url":null,"abstract":"<p><p>Creutzfeldt-Jakob disease (CJD) is a prion-caused condition characterized by progressive neurodegeneration and spongiform structural changes in the brain due to vacuolization and neuronal death. The disease is driven by the accumulation of abnormally folded prion proteins (PrPSc), derived from the normal cellular protein (PrPC). Actin, a fundamental protein essential for maintaining cellular structure and function, is critically involved in the pathophysiology of several neurodegenerative diseases, including Creutzfeldt-Jakob disease (CJD). In CJD, the dysregulation of actin-binding proteins such as cofilin and gelsolin significantly contributes to disease progression by disrupting actin turnover and cytoskeletal reorganization. The actin cytoskeleton is also essential for synaptic plasticity and the functionality of excitatory neurotransmitter receptors, such as glutamate-gated ion channels (AMPA) and N-methyl-D-aspartate (NMDA) receptors. As cytoskeletal integrity deteriorates, receptor dynamics become impaired, leading to disrupted calcium signaling and deficits in cognitive functions. Additionally, actin-based structures, known as tunneling nanotubes (TNTs), play crucial roles in prion spread by facilitating cell-to-cell transfer of prions. Simultaneously, the prion-infected neuronal environment promotes the formation of these structures, further driving disease progression. Targeting actin dynamics through the modulation of actin-binding proteins and related signaling pathways presents a promising avenue for therapeutic development. These approaches hold potential for addressing CJD for broader applications in neurodegenerative diseases characterized by cytoskeletal dysfunction. Current strategies focus on targeting cytoskeletal components such as microtubule stabilizers, actin-binding proteins, HDAC6 inhibitors, and small GTPases, further expanding the possibilities for effective treatments across various neurodegenerative conditions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"15132-15148"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Insight in Cellular and Molecular Signaling Regulation for Neural Differentiation Program.","authors":"Rabia Shahid, Sumreen Begum","doi":"10.1007/s12035-025-05122-x","DOIUrl":"10.1007/s12035-025-05122-x","url":null,"abstract":"<p><p>Numerous neurological conditions impact the brain, spinal cord, and nerves, including neurodegenerative diseases such as Alzheimer's and Parkinson's disease, autoimmune disorders like Multiple sclerosis, seizure disorders such as Epilepsy, and neuropsychiatric disorders like Schizophrenia and Autism spectrum disorders. Neural stem cells (NSCs) exhibit developmental abnormalities linked to the dysregulation of signaling pathways associated with diverse neurological disorders. NSCs can self-renew and differentiate into various neural cell types. NSC holds enormous therapeutic potential for targeting anomalous neural networks, traumatic brain injuries, and stroke. NSC differentiation programs are regulated by multiple elements, comprising growth factors, neurotransmitters, and extracellular matrix components, with intricate orchestration of cellular and molecular signaling pathways. This review aims to provide current information regarding the critical mechanisms of neural signaling circuits with interacting proteins involved in regular neural differentiation programs. The pivotal complex communication channels include the Notch, Wnt, BMP, RA, FGF, EGF, and Hippo signaling pathways. These circuits are implicated in the processes of NSC maintenance, proliferation, and differentiation, which collectively govern neural fate determination. This information can be used to initiate and promote neural regeneration. Based on the contributing factors in each signaling pathway, novel methods can be formulated and implemented for better and more robust neural differentiation programs. Hence, innovative approaches to treating neural disorders through an enhanced understanding of neural differentiation signaling pathways are paving the way for more effective therapeutic strategies.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"15205-15226"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Chronic Photobiomodulation with Transcranial Near-Infrared Laser on Seizure Frequency and Brain Metabolomics of Rats with Pilocarpine-Induced Seizures.","authors":"Fabrizio Dos Santos Cardoso, Ricardo Mario Arida, Eduardo Alves da Silva, Ana Carolina Ribeiro de Oliveira, Wagner Ferreira Dos Santos, Rodrigo Álvaro Brandão Lopes-Martins, Francisco Gonzalez-Lima, Norberto Cysne Coimbra, Sérgio Gomes da Silva","doi":"10.1007/s12035-025-05175-y","DOIUrl":"10.1007/s12035-025-05175-y","url":null,"abstract":"<p><p>Epilepsy is a chronic brain disorder characterized by abnormal and highly synchronous activity of neuronal cells. This condition is often associated with neuronal hyperexcitability and metabolic imbalances in regions such as the neocortex and archicortex (hippocampus). Pharmacological treatment with antiepileptic drugs has been essential in most cases. However, some patients continue to experience seizures despite medication. Consequently, the search for alternative treatments and new therapeutic interventions has garnered significant interest within the medical community. Among these, photobiomodulation (PBM) shows great promise, particularly due to its cerebral and neuroprotective effects. We evaluated and compared the seizure frequency and the neocortical and hippocampal metabolomic profiles of pilocarpine-induced epileptic rats exposed to chronic transcranial photobiomodulation treatment (30 days of treatment) with an 810-nm, 100-mW laser. Our data show that PBM treatment significantly reduced the seizure frequency in rats with pilocarpine-induced seizures. Additionally, significant changes were observed in the metabolomic profiles of the neocortex and hippocampus. In the neocortex, the treatment reduced metabolic pathways associated with excitotoxicity and oxidative stress. In the hippocampus, an increase in phenylalanine concentration was detected. In addition, the reduction in the number of seizures in laser-treated rats with pilocarpine-induced seizures was correlated with lower neocortical lysine concentration. Taken together, our findings indicate that transcranial PBM prevents the increase in seizure frequency in rats with epilepsy and modulates the brain metabolic pathways of epileptic rats.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14063-14078"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy of Intrathecal Platelet-Rich Plasma Administration in Alleviation of Chronic Neuropathic Pain in Rat Model.","authors":"Jaisan Islam, Preeti Kumari Chaudhary, Sanggu Kim, Elina Kc, Young Seok Park, Soochong Kim","doi":"10.1007/s12035-025-05173-0","DOIUrl":"10.1007/s12035-025-05173-0","url":null,"abstract":"<p><p>Chronic neuropathic pain (CNP), marked by various stinging sensations, frequently arises from lumbosacral disorders, where astrocytes in the spinal dorsal horn (SDH) significantly contribute to its persistence. Platelet-rich plasma (PRP) treatment has shown regulatory effects on astrocytic activity in inflammatory and diabetic neuropathy, yet its impact on CNP remains unclear. This study investigates the potential of intrathecal PRP injections for mitigating CNP in a chronic compressed dorsal root ganglion (CCD) rat model. Animals were divided into CCD, sham, and control groups. PRP or phosphate-buffered saline (PBS) was injected intrathecally between the L4-L5 spinal cord. Assessments included mechanical and thermal pain behavioral tests, and in vivo extracellular recordings from the contralateral ventral posterolateral (VPL) thalamus. Additionally, the expression of astrocytic pain mediators in the SDH was analyzed through immunofluorescence. Results showed that the CCD group had significantly lower pain thresholds compared to the sham group. PRP treatment led to improved CNP responses in CCD rats, unlike in the PBS group, highlighting PRP's role in CNP amelioration. Electrophysiology confirmed a notable reduction in VPL thalamic activity post-PRP treatment. Immunofluorescence (IFC) analysis revealed significant increases in neuronal c-fos expression in the DRG and SDH of CCD rats, which were notably reduced following PRP treatment. IFC analysis also indicated decreased expression of pain-transmission-associated astrocyte markers, including glial fibrillary acidic protein (GFAP), pyruvate kinase M2 (PKM2), and high mobility group box-1 protein (HMGB1) in PRP-treated CCD subjects. Thus, we demonstrate that PRP attenuates CNP in a CCD rat model by regulating nociceptive input into the spinothalamic tract through the inhibition of astrocytic activity in SDH, presenting itself as a viable therapy for CNP linked to lumbosacral conditions.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13840-13857"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine can be a Potential Therapeutic Agent in Treatment of Huntington's Disease: A Proposed Mechanistic Insight.","authors":"Seema Sharma, Inderpreet Kaur, Naina Dubey, Neelima Goswami, Sampat Singh Tanwar","doi":"10.1007/s12035-025-05054-6","DOIUrl":"10.1007/s12035-025-05054-6","url":null,"abstract":"<p><p>Huntington's disease (HD) is a genetic neurodegenerative disorder caused by CAG repeat expansion in the HTT gene, producing mutant huntingtin (mHTT) protein. This leads to neuronal damage through protein aggregation, transcriptional dysregulation, excitotoxicity, and mitochondrial dysfunction. mHTT impairs protein clearance and alters gene expression, energy metabolism, and synaptic function. Therapeutic strategies include enhancing mHTT degradation, gene silencing via antisense oligonucleotides and RNAi, promoting neuroprotection through BDNF signaling, and modulating neurotransmitters like glutamate and dopamine. Berberine, a natural isoquinoline alkaloid, has emerged as a promising therapeutic option for HD due to its multifaceted neuroprotective properties. Research indicates that berberine can mitigate the progression of neurodegenerative diseases, including HD, by targeting various molecular pathways. It exhibits antioxidant, anti-inflammatory, and autophagy-enhancing effects, which are crucial in reducing neuronal damage and apoptosis associated with HD. These properties make berberine a potential candidate for therapeutic intervention in HD, as demonstrated in both cellular and animal models. Berberine activates the PI3K/Akt pathway, which is vital for cell survival and neuroprotection. It reduces oxidative stress and neuroinflammation, both of which are implicated in HD pathology. Berberine enhances autophagic processes, promoting the degradation of mutant huntingtin protein, a key pathological feature of HD. In transgenic HD mouse models, berberine administration has been shown to alleviate motor dysfunction and prolong survival. It effectively reduces the accumulation of mutant huntingtin in cultured cells, suggesting a direct impact on the disease's molecular underpinnings. Berberine's safety profile, established through its use in treating other conditions, supports its potential for clinical trials in HD patients. Its ability to modulate neurotransmitter levels and engage multiple signaling pathways further underscores its therapeutic promise. While berberine shows significant potential as a therapeutic agent for HD, further research is necessary to fully elucidate its mechanisms and optimize its clinical application. The current evidence in the review paper, primarily from preclinical studies, provides a strong foundation for future investigations into berberine's efficacy and safety in human HD patients.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14734-14762"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View.","authors":"Naser-Aldin Lashgari, Mahla Khalaji, Pouria Rana, Fatemeh Badrabadi, Mobina Rahnama, Hadis Nasoori, Nazanin Momeni Roudsari, Mohammad Mahdi Khosravi Nia, Hamed Shafaroodi","doi":"10.1007/s12035-025-05097-9","DOIUrl":"10.1007/s12035-025-05097-9","url":null,"abstract":"<p><p>Neurological and psychiatric disorders are considered one of the major problems of today's societies and cause many individual and social problems. Current treatments are effective, but due to their burdens, there is always an effort to introduce novel treatments. Psychedelics, a diverse group of psychoactive compounds, including LSD, psilocybin, DMT, MDMA, and ketamine, have shown potential in modulating neurologic and psychiatric disorders due to several mechanisms. This review investigates the therapeutic potential of psychedelics in both neurologic and neuropsychiatric disorders due to their several mechanisms such as anti-inflammatory, anti-oxidative, and biological properties. This study was conducted across major databases, such as PubMed, Scopus, Web of Science, Google Scholar, and Medline, due to the systematically searched literature including clinical, preclinical, and in vitro studies. Psychedelic compounds such as psilocybin, LSD, and MDMA have demonstrated beneficial effects across various models of neuropsychiatric and neurologic disorders, including depression, PTSD, Alzheimer's disease, and Parkinson's disease. These effects are mediated through multiple mechanisms, including anti-inflammatory actions (e.g., downregulation of cytokines such as IL-6 and TNF-α), antioxidant activity (e.g., induction of SOD), and enhancement of neuroplasticity through increased expression of brain-derived neurotrophic factor such as BDNF. Additionally, psychedelics modulate key neurotransmitter systems, notably increasing synaptic levels of serotonin and dopamine, which are critically involved in mood regulation and cognitive function. Compared to conventional treatments, psychedelics offer faster onset, durable effects, and possible disease-modifying properties, making them promising candidates for future neurotherapeutics.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"15070-15092"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Deinoxanthin on Brain Oxidative Damage and Gut Microbiota in the D-Galactose-Induced Aging Mice.","authors":"Huijuan Su, Yutao Li, Jiayi Wan, Jieyu Lin, Jiayao Wang, Rui Fan, Dingming Liu, Jing Wei, Hongbo Xin, Yuejin Hua, Shengjie Li","doi":"10.1007/s12035-025-05215-7","DOIUrl":"10.1007/s12035-025-05215-7","url":null,"abstract":"<p><p>Deinoxanthin (DX), a special hydroxylated tetraterpenoid synthesized by Deinococcus radiodurans, exhibits robust antioxidative activities in vitro and in vivo. The accumulation of excessive reactive oxygen species (ROS) and free radicals in the body would induce brain oxidative damage, thereby contributing to the process of aging. Whether the administration of DX could protect the brain against oxidative damage in aging is of great interest. In this study, we explored the potential beneficial effects of DX on D-galactose (D-gal)-induced aging mice in vivo, particularly its protective effects on the brain against oxidative damage, and its impact on the gut microbiota of aging mice. We demonstrated that treatment with a low dose (25 mg/kg/day) and a middle dose (50 mg/kg/day) of DX could effectively alleviate motor deficits, reduce the hippocampal pathological changes, suppress microglia and astrocyte activation, and attenuate oxidative stress in D-gal-induced aging mice. However, the treatment with a high dose of DX (100 mg/kg/day) seemed to exacerbate these changes, indicating that excessive DX may exacerbate oxidative damage in aging mice. Furthermore, the administration of appropriate DX could restore the gut microbiota in aging mice, while the high dose of DX further aggravated the disturbance of the gut microbiota in aging mice. Collectively, we conclude that taking DX appropriately may be beneficial in preventing oxidative damage to the brain and improving the gut microbiota in aging mice.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14286-14300"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mTOR-Mediated Protection Against Atrazine-Induced Ferroptosis and Dopaminergic Neurodegeneration in Parkinson's Disease Models.","authors":"Xiaojuan Chen, Zeiyu Du, Huimin Shen, Lianghua Huang, Yuxin Zhu, Yanshu Li","doi":"10.1007/s12035-025-05204-w","DOIUrl":"10.1007/s12035-025-05204-w","url":null,"abstract":"<p><p>Atrazine (ATR) is a widely used herbicide known to induce degeneration of nigrostriatal dopaminergic (DA) neurons, leading to a Parkinson's disease (PD)-like syndrome. Ferroptosis, an iron-dependent non-apoptotic cell death, is implicated in various neurodegenerative diseases, though its specific role in PD remains unclear. In this study, 3657 differentially expressed genes associated with PD from the gene expression database were identified, which are enriched in the ferroptosis pathway. Additionally, ATR-induced SD rats and human SH-SY5Y neuroblastoma cells were used to model PD and explore the effects of mTOR on ferroptosis. The results demonstrated that ATR induces ferroptosis, which can be inhibited by pretreatment with Ferrostatin-1. Furthermore, overexpression of mTOR suppressed ATR-induced damage by activating the GPX4 pathway. These findings suggest that mTOR protects against ATR-induced ferroptosis in PD by modulating the GPX4 pathway, highlighting the potential therapeutic value of targeting mTOR and ferroptosis pathways to mitigate ATR-induced neurotoxicity and PD progression.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14301-14314"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring MAPK Pathways: New Therapeutic Avenues for Treating Alzheimer's Disease.","authors":"Apoorv Sharma, Vandana Mehra, Vijay Kumar, Aklank Jain, Hridayesh Prakash","doi":"10.1007/s12035-025-04919-0","DOIUrl":"10.1007/s12035-025-04919-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is irreversible, progressive, and refractory in nature and is managed very poorly clinically due to very limited treatment outcomes. Unfortunately, most of the multiple clinical trials involving AD patients were unsuccessful in improving the disease prognosis. At the cellular level, many signaling pathways have been proposed to be involved in the sterile/refractory behavior of degenerating neurons in AD. Due to the involvement of p38MAPK in the pathogenesis of Alzheimer's disease, numerous investigations have attempted to determine the beneficial effects of MAPK targeting on memory, inflammatory programming of the brain, and synaptic plasticity. In view of this, various clinical trials involving several MAPK inhibitors (with good safety profiles and few side effects) have yielded positive results in AD patients, suggesting that MAPK targeting may be effective for reducing the pathogenesis of AD, but due to selectivity, dosing, and patient stratification, this aspect still needs further development. In view of their selectivity and off-target effects, only a few MAPK inhibitors have been employed in clinical trials against AD, indicating the scope of their development in this area. Therefore, this study focused on MAPK-based interventions as an upcoming and innovative approach for alleviating AD, with a special emphasis on clinical studies.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14315-14343"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}