Metabolic brain disease最新文献

{"title":"Emerging role of adaptive immunity in diabetes-induced cognitive impairment: from the periphery to the brain.","authors":"Genhui Yang, Runtao Su, Jie Bu, Ying Li, Xueling Lin, Jiahui Jin, Yanjun Zhang, Pengwei Zhuang, Hong Guo, Qingsheng Yin","doi":"10.1007/s11011-025-01532-x","DOIUrl":"10.1007/s11011-025-01532-x","url":null,"abstract":"<p><p>Diabetic cognitive impairment (DCI) is a central nervous system complication induced by peripheral metabolic dysfunction of diabetes mellitus. Cumulative studies have shown that neuro-immune crosstalk is involved in the pathological progression of DCI. However, current studies mostly focus on the interaction between innate immunity cells and neurons, while ignoring the role of adaptive immunity cells in DCI. Notably, recent studies have revealed adaptive immune cells are involved in cognitive development and the progression of neurodegenerative diseases. Equally important, accumulated past studies have also shown that diabetic patients experience imbalanced peripheral adaptive immune homeostasis and disrupted transmission of adaptive immune cells to the central system. Therefore, this review first updated the cognitive mechanism of adaptive immune regulation, and then summarized the contribution of adaptive immunity to DCI from the aspects of peripheral adaptive immune homeostasis, transmission pathways, and brain tissue infiltration. Furthermore, we also summarized the potential of anti-diabetic drugs to regulate adaptive immunity, and looked forward to the potential value of regulatory adaptive immunity in the prevention and treatment of DCI, to provide a new strategy for the prevention and treatment of DCI.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"102"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug delivery strategies for the treatment of relapse behavior in substance use disorder- A systematic review.","authors":"Megha Sihag, Manasi Varma, Ranjana Bhandari, Andrew J Lawrence","doi":"10.1007/s11011-024-01492-8","DOIUrl":"10.1007/s11011-024-01492-8","url":null,"abstract":"<p><p>Substance use disorders (SUDs) pose a significant global health challenge, with relapse being a major obstacle in achieving successful treatment outcomes. In recent years, drug delivery strategies have emerged as promising tools to improve treatment efficacy and patient compliance in the context of SUD. Here we explore a diverse range of drug delivery strategies that have been investigated for addressing relapse behavior in SUD. By examining a wide array of clinical and preclinical studies, this review highlights the advances made in drug delivery technologies in the hopes of aiding future research to further establish novel systems. The present systematic review has been created after gathering data from multiple databases including Google Scholar, PubMed and Cochrane, taking into account both review and research (preclinical and clinical) studies along with other systematic reviews and meta-analyses. Relevant articles have been categorized into those pertaining to opioid use disorder, alcohol use disorder and tobacco use disorder. Substance use disorders are a global health problem, with tobacco use associated with the highest mortality, followed by alcohol and opioids. Conventional drug delivery options, such as oral medication have a number of disadvantages, such as low compliance. To tackle these challenges, multiple novel strategies such as sustained release implants, transdermal patches and liquid crystal-based injections have been developed. This systematic review presents a concise view of the strategies already available, as well as those currently undergoing trials. By doing so, the authors hope to stimulate further research to help overcome the challenges in treating SUDs.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"104"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ammonia and beyond - biomarkers of hepatic encephalopathy.","authors":"Juan-José Gallego, María-Pilar Ballester, Alessandra Fiorillo, Franc Casanova-Ferrer, Adrià López-Gramaje, Amparo Urios, Yaiza María Arenas, María-Pilar Ríos, Lucía Durbán, Javier Megías, Teresa San-Miguel, Salvador Benlloch, Paloma Lluch, Rajiv Jalan, Carmina Montoliu","doi":"10.1007/s11011-024-01512-7","DOIUrl":"10.1007/s11011-024-01512-7","url":null,"abstract":"<p><p>Ammonia is a product of amino acid metabolism that accumulates in the blood of patients with liver cirrhosis, leading to neurotoxic effects and hepatic encephalopathy (HE). HE manifestations can range from mild, subclinical disturbances in cognition, or minimal HE (mHE) to gross disorientation and coma, a condition referred to as overt HE. Many blood-based biomarkers reflecting these neurotoxic effects of ammonia and liver disease can be measured in the blood allowing the development of new biomarkers to diagnose cirrhosis patients at risk of developing HE. The effect of ammonia on the brain is modulated by severity of systemic inflammation, and both hyperammonemia and inflammation can induce oxidative stress, which may mediate the neurological alterations associated to HE. This review aims to provide the latest evidence on biomarkers of HE beyond ammonia. We present different approaches to predict overt HE based on the combination of blood ammonia with some analytical and clinical parameters. Magnetic resonance analysis of brain images could also provide sensitive diagnostic biomarkers based on neuroimaging parameters. Some reports suggest that markers of systemic inflammation, oxidative stress, and central nervous system-derived components, may serve as additional biomarkers of HE. The involvement of extracellular vesicles and microbiota in the pathophysiology of mHE and HE has recently acquired importance and it would be interesting to explore their usefulness as early biomarkers of the disease. It is important to have a biomarker or a combination of them for early diagnosis of mHE to improve its treatment and prevent progression to overt HE.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"100"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insight into neuroprotective effect of standardized ginger chemo varieties from Manipur, India in scopolamine induced learning and memory impaired mice.","authors":"Suparna Ghosh, Bhaskar Das, Sandipan Jana, Keithellakpam Ojit Singh, Nanaocha Sharma, Pulok K Mukherjee, Pallab Kanti Haldar","doi":"10.1007/s11011-025-01535-8","DOIUrl":"10.1007/s11011-025-01535-8","url":null,"abstract":"<p><p>Alzheimer's disease is a complex neurodegenerative disease characterized by progressive decline in cognitive function and behaviour. Ginger is the rhizome of the plant Zingiber officinale Roscoe, has been an important ingredient of many Ayurveda formulations to treat neurological disorders. The present study aims to estimate the variation of 6-gingerol content in nine different ginger samples collected from Manipur, India, investigate the neuroprotective potential of the most potent ginger sample against scopolamine-induced cognitively impaired mice, and validate the therapeutic claim by molecular docking analysis. High Performance Thin Layer Chromatography (HPTLC) analysis suggested that the sample GV6 had the highest 6-gingerol content with potent in vitro acetylcholnesterase (AChE) (IC50 = 336.10 µg/mL) and butyrylcholinesterase (BChE) (IC50 = 411.73 µg/mL) enzyme inhibitory activity. The neuroprotective potential of GV6 was tested in scopolamine-induced cognitively impaired mice (200 and 400 mg/kg). The behavioral analysis showed that GV6 alleviated the spatial recognition, and short-term and long-term memory in the experimental mice model. GV6 significantly improved brain AChE and BChE activity, acetylcholine (ACh) level, markedly alleviated the antioxidant parameters, and reversed the neuroinflammation. Brain histopathological observations confirmed the presence of organized nerve fibers, improvement of neuronal cell density, and reverse the nucleus shrinkage. Further molecular docking analysis showed that 6-gingerol and galantamine exhibited stable interaction with AChE (-7.5 and - 7.3 kcaL/moL) and BChE (-7.3 and - 8.5 kcaL/moL). The present study emphasizes the quality-related therapeutic importance of ginger samples from Northeast India and demonstrates that administration of GV6 may improve brain cognitive functions by restoring neurotransmitter levels and inflammatory and antioxidant parameters in scopolamine-induced cognitively impaired mice.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"101"},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genistein-3'-sodium sulfonate suppresses NLRP3-mediated cell pyroptosis after cerebral ischemia.","authors":"Yunling Yu, Xinglan Liao, Kehui Xing, Ziyu Xie, Ningyuan Xie, Yinwen He, Zhihua Huang, Xiaolu Tang, Ruizhen Liu","doi":"10.1007/s11011-025-01530-z","DOIUrl":"10.1007/s11011-025-01530-z","url":null,"abstract":"<p><p>Cerebral ischemia-induced pyroptosis contributes to the dissemination of neuroinflammation, and Nod-like receptor protein-3 (NLRP3) inflammasome plays a key role in this process. Previous studies have indicated that Genistein-3'-sodiumsulfonate (GSS) can inhibit neuroinflammation caused by cerebral ischemia, exert cerebroprotective effects, but its specific mechanism has not been comprehensively understood. The aim of this study was to explore the effect of GSS on ischemic stroke-induced cell pyroptosis. SD rats were randomly assigned to Sham group, transient middle cerebral artery occlusion (tMCAO) group, and tMCAO + GSS group. The open field test (OFT) was utilized to assess animals' spontaneous movement and anxiety-like behavior. Immunofluorescence was adopted to observe nod-like receptor pyrin domain containing 3 (NLRP3)/neuronal nuclei (NeuN) double-positive cells in the ischemic penumbra of each group. Western blot (WB) was conducted to detect levels of NLRP3 inflammasomes and pyroptosis-related proteins in the ischemic cortex tissue. Furthermore, the G protein-coupled estrogen receptor 1 (GPER1) inhibitor G15 was administered to monitor tMCAO rats' motor function, emotional state, and NLRP3 inflammasome activation. Compared with the Sham group, rats in the tMCAO group exhibited significant motor dysfunction and anxiety, increased NLRP3⁺/NeuN⁺ co-expressing cells in the ischemic penumbra, and elevated levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), pro-cysteinyl aspartate specific proteinase-1 (pro-caspase-1), cleaved-cysteinyl aspartate specific proteinase-1 (cleaved-caspase-1), gasdermin D (GSDMD), GSDMD-N-terminal domain (GSDMD-N), interleukin (IL)-1β, and IL-18 in the ischemic cortex. Treatment with GSS reversed these trends. Additionally, post G15 treatment, the therapeutic effects of GSS were reversed. GSS may inhibit NLRP3 inflammasome activation via GPER1, reducing membrane perforation and pro-inflammatory cytokine secretion, suppressing cell pyroptosis, and mitigating neuroinflammation, thereby improving chronic motor dysfunction and anxiety in tMCAO rats. Our study uncovers a potential novel mechanism for GSS treatment in ischemic stroke and provides new ideas for the treatment of ischemic stroke.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"99"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.","authors":"Noah Gladen-Kolarsky, Cody J Neff, Wyatt Hack, Mikah S Brandes, Jack Wiedrick, Roberto Meza-Romero, Denesa R Lockwood, Joseph F Quinn, Halina Offner, Arthur A Vandenbark, Nora E Gray","doi":"10.1007/s11011-024-01433-5","DOIUrl":"10.1007/s11011-024-01433-5","url":null,"abstract":"<p><p>Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression. Here, we evaluate its effects in amyloid-β (Aβ) overexpressing mice. 5xFAD mice and their wild type littermates were treated with DRhQ (100 µg) or vehicle for 4 weeks. DRhQ improved cognition and cortical mitochondrial function in both male and female 5xFAD mice. Aβ plaque burden in 5xFAD animals was not robustly impacted by DRhQ treatment in either the hippocampus or the cortex. Cortical microglial activation was similarly not apparently affected by DRhQ treatment, although in the hippocampus there was evidence of a reduction in activated microglia for female 5xFAD mice. Future studies are needed to confirm this possible sex-dependent response on microglial activation, as well as to optimize the dose and timing of DRhQ treatment and gain a better understanding of its mechanism of action in AD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"95"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TeMac™ ameliorates memory impairment and cholinergic dysfunction in rats induced by scopolamine.","authors":"Bruno Dupon Akamba Ambamba, Fils Armand Ella, Dany Joël Ngassa Ngoumen, Janvier Aime Fotso Youovop, Guy Roussel Nguemto Takuissu, Ruth Edwige Kemadjou Dibacto, Martin Fonkoua, Damaris Enyegue Mandob, Sefirin Djiogue, Judith Laure Ngondi","doi":"10.1007/s11011-024-01521-6","DOIUrl":"10.1007/s11011-024-01521-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days. TeMac™ at 400 mg/kg body weight was orally administrated 60 min after scopolamine. Donepezil was used as a reference drug. The cognitive deficits were assessed by the Morris Water Maze and novel object recognition tests. After killing the rats, brains were immediately collected and used to carry out cholinesterase enzyme activity and histopathological analyses. Liquid chromatography-mass spectrometry (LC-MS) characterization of the TeMac™ was carried out and the identified molecules were tested in silico for their ability to cross the Blood-Brain Barrier (BBB) and inhibit acetylcholinesterase using molecular docking. The administration of the TeMac™ led to the prevention of memory deficits in rats by reducing significantly the cholinesterase enzymes activities and protecting against morphological alterations and loss of neurons in hippocampus. Seven major compounds were identified in TeMac™. Molecular docking simulations confirm the ability of oleaterminaloic acid B and stigmasterol to cross the BBB and interact with peripheral site and the acyl pocket of acetylcholinesterase. All these observations suggest that TeMac™ can therefore be used as an alternative for the management of AD-related cognitive impairments.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"98"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes.","authors":"Cifuentes-Mendiola Saúl Ernesto, Sólis-Suarez Diana Laura, Pérez-Martínez Isaac Obed, Andrade-González Rey David, García-Gama Jahaziel Eloy, García-Hernández Ana Lilia","doi":"10.1007/s11011-024-01454-0","DOIUrl":"10.1007/s11011-024-01454-0","url":null,"abstract":"<p><p>LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.</p><p><strong>Material and methods: </strong>4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control. T2D was induced by low doses of streptozotocin and a high-carbohydrate diet. LCN2 blockade was performed by intraperitoneal administration of a polyclonal anti-LCN2 antibody. We analyzed metabolic parameters, food intake, feeding patterns, and serum LCN2 and leptin concentrations. In another group of intact or T2D mice, we analyzed the effect of blocking LCN2 and recombinant LCN2 on food consumption in a fasting-refeeding test and, the expression of cFOS and LCN2 in brain sections, specifically in the hypothalamus, piriform cortex, visceral area, arcuate nucleus and caudate-putamen.</p><p><strong>Results: </strong>T2D caused an increase in serum LCN2, without alterations in Ad libitum feeding, but with changes in the feeding pattern associated with alterations in LCN2-cFOS signalling in hypothalamic and non-hypothalamic brain regions. Blocking LCN2 improved metabolic parameters, increased Ad libitum feeding, and restored the feeding pattern after fasting, which is associated with enhanced LCN2 signalling in the brain.</p><p><strong>Conclusions: </strong>Blocking LCN2 restores metabolic health and normalizes the pattern of food consumption by normalizing LCN2 signalling in different brain regions.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"97"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Citrobacter rodentium promotes brain cognitive dysfunction of type 2 diabetes mice by activating FXR mediated gut barrier damage.","authors":"Yuan Li, Song-Tao Chen, Yao-Yuan Zhang, Jin-Feng Qin, Xiao Zhu, Kai Yin","doi":"10.1007/s11011-025-01529-6","DOIUrl":"10.1007/s11011-025-01529-6","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is an important risk factor for brain cognitive impairment, but the specific mechanism is still unclear. The imbalance of gut microbiota under pathological conditions (such as an increase in pathogenic bacteria) may be involved in the occurrence of various diseases. The purpose of this study is to investigate the effect of increased abundance of gut Citrobacter rodentium on cognitive function in T2D mice. Our results indicate that an increase in the abundance of Citrobacter rodentium leads to impaired intestinal barrier, elevated expression of inflammatory factors in blood and brain tissue, and promotes cognitive impairment in T2D mice. The specific pathway involves activation of farnesol X receptor (FXR) expression-mediated intestinal barrier dysfunction. The use of intestinal mucosal protectants and FXR inhibitors improved intestinal barrier function and brain cognitive function. Therefore, the research results provide a mechanistic link between the increased abundance of Citrobacter in the gut of T2D mice and brain cognitive function, and provide a reference for the occurrence of brain cognitive dysfunction in T2D.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"96"},"PeriodicalIF":3.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the potential of the ketogenic diet in autism spectrum disorder: metabolic, genetic, and therapeutic insights.","authors":"Alexa Schrickel, Jop Groeneweg, Eline Dekeyster","doi":"10.1007/s11011-024-01518-1","DOIUrl":"10.1007/s11011-024-01518-1","url":null,"abstract":"<p><p>Current treatment approaches for Autism spectrum disorder (ASD) primarily focus on symptom management rather than addressing underlying dysfunctions. The ketogenic diet (KD), a high-fat, low-carbohydrate diet inducing nutritional ketosis, has shown promise in treating epilepsy and may offer therapeutic benefits for ASD by modulating metabolic and neuroprotective pathways. This review examined the potential impact of KD on underlying mechanisms in ASD. While evidence from human studies on underlying mechanisms is limited, animal research has shown a large overlap of mechanisms modulated by KD and dysfunctions in ASD. As such, targeting multiple disrupted pathways at once, KD presents a potential multifaceted treatment approach for ASD. However, more evidence from human studies is needed on the effectiveness of KD in the modulation of underlying dysfunctions in ASD. Additionally, precision medicine approaches could help identify individuals who would benefit most from the intervention, potentially extending its use to other psychiatric conditions with similar metabolic patterns. Consequently, KD interventions might show the potential to induce a drastic paradigm shift in understanding and treating ASD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"94"},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11711257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}