Neurochemical Research最新文献

{"title":"High-fat and High-sucrose Diet-induced Hypothalamic Inflammation Shows Sex Specific Features in Mice","authors":"Gabriela C. De Paula,&nbsp;Rui F. Simões,&nbsp;Alba M. Garcia-Serrano,&nbsp;João M. N. Duarte","doi":"10.1007/s11064-024-04243-4","DOIUrl":"10.1007/s11064-024-04243-4","url":null,"abstract":"<div><p>Hypothalamic inflammation underlies diet-induced obesity and diabetes in rodent models. While diet normalization largely allows for recovery from metabolic impairment, it remains unknown whether long-term hypothalamic inflammation induced by obesogenic diets is a reversible process. In this study, we aimed at determining sex specificity of hypothalamic neuroinflammation and gliosis in mice fed a fat- and sugar-rich diet, and their reversibility upon diet normalization. Mice were fed a 60%-fat diet complemented by a 20% sucrose drink (HFHSD) for 3 days or 24 weeks, followed by a third group that had their diet normalized for the last 8 weeks of the study (reverse diet group, RevD). We determined the expression of pro- and anti-inflammatory cytokines, and of the inflammatory cell markers IBA1, CD68, GFAP and EMR1 in the hypothalamus, and analyzed morphology of microglia (IBA-1⁺ cells) and astrocytes (GFAP⁺ cells) in the arcuate nucleus. After 3 days of HFHSD feeding, male mice showed over-expression of IL-13, IL-18, IFN-γ, CD68 and EMR1 and reduced expression of IL-10, while females showed increased IL-6 and IBA1 and reduced IL-13, compared to controls. After 24 weeks of HFHSD exposure, male mice showed a general depression in the expression of cytokines, with prominent reduction of TNF-α, IL-6 and IL-13, but increased TGF-β, while female mice showed over-expression of IFN-γ and IL-18. Furthermore, both female and male mice showed some degree of gliosis after HFHSD feeding for 24 weeks. In mice of both sexes, diet normalization after prolonged HFHSD feeding resulted in partial neuroinflammation recovery in the hypothalamus, but gliosis was only recovered in females. In sum, HFHSD-fed mice display sex-specific inflammatory processes in the hypothalamus that are not fully reversible after diet normalization.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3356 - 3366"},"PeriodicalIF":3.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278591","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":"Ferulic Acid-Loaded Nanostructure Maintains Brain Levels of ACh, Glutamate, and GABA and Ameliorates Anxiety and Memory Impairments Induced by the d-Galactose Aging Process in Rats","authors":"Domenika R. Rossato,&nbsp;Jéssica L. O. Rosa,&nbsp;Murilo B. Fontoura,&nbsp;Leana E. M. de Souza,&nbsp;Tielle M. de Almeida,&nbsp;Kathiane B. Kudrna,&nbsp;Scheila R. Schaffazick,&nbsp;Cristiane B. da Silva,&nbsp;Letícia Birk,&nbsp;Sarah Eller,&nbsp;Tiago F. de Oliveira,&nbsp;Marilise E. Burger","doi":"10.1007/s11064-024-04248-z","DOIUrl":"10.1007/s11064-024-04248-z","url":null,"abstract":"<div><p>Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male <i>Wistar</i> adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3383 - 3395"},"PeriodicalIF":3.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278590","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":"Neuroprotective Properties of Coriander-Derived Compounds on Neuronal Cell Damage under Oxidative Stress-Induced SH-SY5Y Neuroblastoma and in Silico ADMET Analysis","authors":"Papitcha Jongwachirachai,&nbsp;Waralee Ruankham,&nbsp;Setthawut Apiraksattayakul,&nbsp;Saruta Intharakham,&nbsp;Veda Prachayasittikul,&nbsp;Wilasinee Suwanjang,&nbsp;Virapong Prachayasittikul,&nbsp;Supaluk Prachayasittikul,&nbsp;Kamonrat Phopin","doi":"10.1007/s11064-024-04239-0","DOIUrl":"10.1007/s11064-024-04239-0","url":null,"abstract":"<div><p>An imbalance between reactive oxygen species (ROS) production and antioxidant defense driven by oxidative stress and inflammation is a critical factor in the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Coriander (<i>Coriandrum sativum</i> L.), a culinary plant in the <i>Apiaceae</i> family, displays various biological activities, including anticancer, antimicrobial, and antioxidant effects. Herein, neuroprotective properties of three major bioactive compounds derived from coriander (i.e., linalool, linalyl acetate, and geranyl acetate) were investigated on hydrogen peroxide-induced SH-SY5Y neuroblastoma cell death by examining cell viability, ROS production, mitochondrial membrane potential, and apoptotic profiles. Moreover, underlying mechanisms of the compounds were determined by measuring intracellular sirtuin 1 (SIRT1) enzyme activity incorporated with molecular docking. The results showed that linalool, linalyl acetate, and geranyl acetate elicited their neuroprotection against oxidative stress <i>via</i> protecting cell death, reducing ROS production, preventing cell apoptosis, and modulating SIRT1 longevity. Additionally, in silico pharmacokinetic predictions indicated that these three compounds are drug-like agents with a high probability of absorption and distribution, as well as minimal potential toxicities. These findings highlighted the potential neuroprotective linalool, linalyl acetate, and geranyl acetate for developing alternative natural compound-based neurodegenerative therapeutics and prevention.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3308 - 3325"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04239-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258624","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":"Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases","authors":"Yi Zhang,&nbsp;Ziyu Wang,&nbsp;Fenglian Xu,&nbsp;Zijun Liu,&nbsp;Yu Zhao,&nbsp;Lele Zixin Yang,&nbsp;Weirong Fang","doi":"10.1007/s11064-024-04241-6","DOIUrl":"10.1007/s11064-024-04241-6","url":null,"abstract":"<div><p>Neurons are the primary cells responsible for information processing in the central nervous system (CNS). However, they are vulnerable to damage and insult in a variety of neurological disorders. As the most abundant glial cells in the brain, astrocytes provide crucial support to neurons and participate in synapse formation, synaptic transmission, neurotransmitter recycling, regulation of metabolic processes, and the maintenance of the blood-brain barrier integrity. Though astrocytes play a significant role in the manifestation of injury and disease, they do not work in isolation. Cellular interactions between astrocytes and neurons are essential for maintaining the homeostasis of the CNS under both physiological and pathological conditions. In this review, we explore the diverse interactions between astrocytes and neurons under physiological conditions, including the exchange of neurotrophic factors, gliotransmitters, and energy substrates, and different CNS diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, traumatic brain injury, and multiple sclerosis. This review sheds light on the contribution of astrocyte-neuron crosstalk to the progression of neurological diseases to provide potential therapeutic targets for the treatment of neurological diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3187 - 3207"},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04241-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258623","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":"Correction: Nuclear Medicine Imaging Techniques in Glioblastomas","authors":"Emirhan Harbi,&nbsp;Michael Aschner","doi":"10.1007/s11064-024-04247-0","DOIUrl":"10.1007/s11064-024-04247-0","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 11","pages":"3014 - 3014"},"PeriodicalIF":3.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278589","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":"New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD)","authors":"Reza Ghaffarzadegan,&nbsp;Shahin Akhondzadeh,&nbsp;Zahra Nikasa,&nbsp;Shadi Hajizamani,&nbsp;Saba Mehrabanifar,&nbsp;Iman Cheraghi,&nbsp;Salar Vaseghi","doi":"10.1007/s11064-024-04242-5","DOIUrl":"10.1007/s11064-024-04242-5","url":null,"abstract":"<div><p>Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3226 - 3243"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258625","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":"Mirtazapine Improves Locomotor Activity and Attenuates Neuropathic Pain Following Spinal Cord Injury in Rats via Neuroinflammation Modulation","authors":"Seyed Hadi Aghili,&nbsp;Mohammad Amin Manavi,&nbsp;Mohammad Panji,&nbsp;Mehri Farhang Ranjbar,&nbsp;Ramin Abrishami,&nbsp;Ahmad Reza Dehpour","doi":"10.1007/s11064-024-04240-7","DOIUrl":"10.1007/s11064-024-04240-7","url":null,"abstract":"<div><p>Neuroinflammation-related locomotor deficits and neuropathic pain are expected outcomes of spinal cord injury (SCI). The atypical antidepressant mirtazapine has exhibited potential neuroprotective and anti-inflammatory effects. This research aims to investigate the impacts of mirtazapine on post-SCI neuropathic pain and locomotor recovery, with a particular focus on neuroinflammation. The study utilized 30 male Wistar rats divided into five groups: Sham, SCI with vehicle treatment, and SCI administered with mirtazapine (3, 10, and 30 mg/kg/day, <i>ip</i>, for one week). Locomotor activity was assessed using the Basso, Beattie, and Bresnahan (BBB) scale. Mechanical, thermal, and cold allodynia were assessed using von-Frey filaments, tail flick latency, and the acetone test, respectively. ELISA was utilized to measure cytokines, while Western blotting was used to determine TRPV1 channel, 5-HT2A receptor, NLRP3, and iNOS expression. Histopathological analyses were also examined, including hematoxylin and eosin (H&amp;E) and Luxol fast blue (LFB) staining. Mirtazapine (10 and 30 mg/kg/day) significantly improved locomotor recovery according to BBB score. It attenuated mechanical, thermal, and cold allodynia post-SCI. Moreover, it decreased pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-18, while increasing anti-inflammatory cytokine IL-4 and IL-10. Furthermore, it downregulated iNOS, NLRP3, and TRPV1 expression and upregulated the 5-HT2A receptor. H&amp;E and LFB staining further revealed attenuated tissue damage and decreased demyelination. Our findings suggest that mirtazapine can alleviate neuropathic pain and reinforce locomotor recovery post-SCI by modulating neuroinflammatory responses, NLRP3, iNOS, TRPV1 channel, and 5-HT2A receptor expression.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3326 - 3341"},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258627","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":"Neuromedin U Neurons in the Edinger–Westphal Nucleus Respond to Alcohol Without Interfering with the Urocortin 1 Response","authors":"Mireia Medrano,&nbsp;Wissal Allaoui,&nbsp;Ra’fat Ehab Salim Haddad,&nbsp;Leila Makrini-Maleville,&nbsp;Emmanuel Valjent,&nbsp;Ilse Smolders,&nbsp;Viktória Kormos,&nbsp;Balázs Gaszner,&nbsp;Dimitri De Bundel","doi":"10.1007/s11064-024-04238-1","DOIUrl":"10.1007/s11064-024-04238-1","url":null,"abstract":"<div><p>The Edinger–Westphal nucleus (EW) is a midbrain nucleus composed of a preganglionic, cholinergic subpopulation and a densely clustered peptidergic subpopulation (EWcp). The EWcp is one of the few brain regions that show consistent induction of FOS following voluntary alcohol intake. Previous results in rodents point to urocortin 1 (UCN1) as one of the peptides most involved in the control of ethanol intake and preference. Notably, the functions described for UCN1, such as reward processing, stress coping or the regulation of feeding behavior are similar to those described for the neuropeptide neuromedin U (NMU). Interestingly, NMU has been recently associated with the modulation of alcohol-related behaviors. However, little is known about the expression and functionality of NMU neurons in alcohol-responsive areas. In this study, we used the recently developed Nmu-Cre knock-in mouse model to examine the expression of NMU in the subaqueductal paramedian zone comprising the EWcp. We delved into the characterization and co-expression of NMU with other markers already described in the EWcp. Moreover, using FOS as a marker of neuronal activity, we tested whether NMU neurons were sensitive to acute alcohol administration. Overall, we provided novel insights on NMU expression and functionality in the EW region. We showed the presence of NMU within a subpopulation of UCN1 neurons in the EWcp and demonstrated that this partial co-expression does not interfere with the responsivity of UCN1-containing cells to alcohol. Moreover, we proposed that the UCN1 content in these neurons may be influenced by sex.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3277 - 3296"},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04238-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192635","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":"Activation of the LKB1/AMPK/HIF-1α Pathway by Metformin to Promote Neovascularisation in Cerebral Ischaemia","authors":"Hongguang Chen,&nbsp;Yuting Yuan,&nbsp;Yue Zhang,&nbsp;Xiufen Liu,&nbsp;Qingjie Chen,&nbsp;Chao Liu,&nbsp;Qing Yao","doi":"10.1007/s11064-024-04235-4","DOIUrl":"10.1007/s11064-024-04235-4","url":null,"abstract":"<div><p>As a difficult-to-treat neurological condition, cerebral ischemia is currently limited to treatments such as intravenous recombinant tissue plasminogen activator thrombolysis and thrombectomy. Metformin, a potent antidiabetic drug, has been reported to have an independent function in enhancing the prognosis of stroke patients, in addition to its glucose-lowering effects. However, the mechanism of action of metformin in this context remains unclear. In vivo, a rat model of permanent middle cerebral artery occlusion was established, and after administration of a low dose of 10.5 mg/mL metformin, infarct area was measured by TTC staining, and cortical blood flow was determined by laser Doppler imaging. In vitro, the study established human umbilical vein endothelial cells treated with cobalt chloride. Immunofluorescence, immunohistochemistry, and Western blot experiments were performed to observe the expression of angiogenic factors, tight junction proteins, and apoptotic factors. A TUNEL assay was utilized to appraise cell death by apoptosis. A tube formation assay and scratch assay were conducted to determine the endothelial neovascularization status. Animal experiments have revealed that the administration of the AMPK activator metformin significantly reduced the infarct area, promoted the expression of angiogenic factors, and maintained the stability of tight junction proteins in endothelial cells. Moreover, metformin reduces nerve cells apoptosis by affecting the expression of the apoptotic protein cleaved-caspase3 via the HIF-1α pathway. In vitro, the LKB1/AMPK signaling pathway is activated after hypoxic stimulation, attaining its peak within the early stages of hypoxia (1–12 h) and gradually weakening thereafter. The administration of AMPK pharmacological agonists (between 36 and 48 h) can enhance AMPK activity, which can lead to the expression of angiogenic factors, maintain the stability of tight-junction proteins in endothelial cells, and facilitate endothelial cell migration and vascular structure formation. Conversely, the AMPK inhibitors exert the opposite effects. The activation of the LKB1/AMPK/HIF-1α signaling pathway by metformin in cerebral ischemia contributes to angiogenesis, promotes tissue repair in the injured area, and enhances neurologically functional symptoms.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3263 - 3276"},"PeriodicalIF":3.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138958","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":"A Retrospective Tribute to Dr. Harish Pant (1938–2023) and His Seminal Work on Cyclin Dependent Kinase 5","authors":"Bradford Hall,&nbsp;Niranjana Amin,&nbsp; Veeranna,&nbsp;Shin-ichi Hisanaga,&nbsp;Ashok. B. Kulkarni","doi":"10.1007/s11064-024-04234-5","DOIUrl":"10.1007/s11064-024-04234-5","url":null,"abstract":"<div><p>Dr. Harish Chandra Pant was Chief of the Section on Neuronal Cytoskeletal Protein Regulation within the National Institute of Neurological Disorders and Stroke at the NIH. A main focus of his group was understanding the mechanisms regulating neuronal cytoskeletal phosphorylation. Phosphorylation of neurofilaments can increase filament stability and confer resistance to proteolysis, but aberrant hyperphosphorylation of neurofilaments can be found in the neurofibrillary tangles that are seen with neurodegenerative diseases like Alzheimer disease (AD). Through his work, Harish would inevitably come across cyclin dependent kinase 5 (Cdk5), a key kinase that can phosphorylate neurofilaments at KSPXK motifs. Cdk5 differs from other Cdks in that its activity is mainly in post-mitotic neurons rather than being involved in the cell cycle in dividing cells. With continued interest in Cdk5, Harish and his group were instrumental in identifying important roles for this neuronal kinase in not only neuronal cytoskeleton phosphorylation but also in neuronal development, synaptogenesis, and neuronal survival. Here, we review the accomplishments of Harish in characterizing the functions of Cdk5 and its involvement in neuronal health and disease.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"49 12","pages":"3181 - 3186"},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131551","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}