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| 1 | Signalling pathways in autism spectrum disorder:mechanisms and therapeutic implications显示文摘Autism spectrum disorder(ASD)is a prevalent and complex neurodevelopmental disorder which has strong genetic basis.Despite the rapidly rising incidence of autism,little is known about its aetiology,risk factors,and disease progression.There are currently neither validated biomarkers for diagnostic screening nor specific medication for autism.Over the last two decades,there have been remarkable advances in genetics,with hundreds of genes identified and validated as being associated with a high risk for autism.The convergence of neuroscience methods is becoming more widely recognized for its significance in elucidating the pathological mechanisms of autism.Efforts have been devoted to exploring the behavioural functions,key pathological mechanisms and potential treatments of autism.Here,as we highlight in this review,emerging evidence shows that signal transduction molecular events are involved in pathological processes such as transcription,translation,synaptic transmission,epigenetics and immunoinflammatory responses.This involvement has important implications for the discovery of precise molecular targets for autism.Moreover,we review recent insights into the mechanisms and clinical implications of signal transduction in autism from molecular,cellular,neural circuit,and neurobehavioural aspects.Finally,the challenges and future perspectives are discussed with regard to novel strategies predicated on the biological features of autism. | Chen-Chen Jiang Li-Shan Lin Sen Long Xiao-Yan Ke Kohji Fukunaga Ying-Mei Lu Feng Han | 2022 | Signal Transduction and Targeted Therapy2022，7，8： | 3 |
| 2 | Fatty acid-binding protein 7 triggersα-synuclein oligomerization in glial cells and oligodendrocytes associated with oxidative stress显示文摘We previously show that fatty acid-binding protein 3(FABP3)triggersα-synuclein(Syn)accumulation and induces dopamine neuronal cell death in Parkinson disease mouse model.But the role of fatty acid-binding protein 7(FABP7)in the brain remains unclear.In this study we investigated whether FABP7 was involved in synucleinopathies.We showed that FABP7 was co-localized and formed a complex with Syn in Syn-transfected U251 human glioblastoma cells,and treatment with arachidonic acid(100 M)significantly promoted FABP7-induced Syn aggregation,which was associated with cell death.We demonstrated that synthetic FABP7 ligand 6 displayed a high affinity against FABP7 with Kd value of 209 nM assessed in 8-anilinonaphthalene-1-sulfonic acid(ANS)assay;ligand 6 improved U251 cell survival via disrupting the FABP7–Syn interaction.We showed that activation of phospholipase A2(PLA2)by psychosine(10 M)triggered oligomerization of endogenous Syn and FABP7,and induced cell death in both KG-1C human oligodendroglia cells and oligodendrocyte precursor cells(OPCs).FABP7 ligand 6(1 M)significantly decreased Syn oligomerization and aggregation thereby prevented KG-1C and OPC cell death.This study demonstrates that FABP7 triggersα-synuclein oligomerization through oxidative stress,while FABP7 ligand 6 can inhibit FABP7-induced Syn oligomerization and aggregation,thereby rescuing glial cells and oligodendrocytes from cell death. | An Cheng Yi-fei Wang Yasuharu Shinoda Ichiro Kawahata Tetsunori Yamamoto Wen-bin Jia Hanae Yamamoto Tomohiro Mizobata Yasushi Kawata Kohji Fukunaga | 2022 | Acta Pharmacologica Sinica2022，43，3： | 2 |
| 3 | Nobiletin improves brain ischemia-induced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation显示文摘 | Yui Yamamoto Norifumi Shioda Feng Han Shigeki Moriguchi Akira Nakajima Akihito Yokosuka Yoshihiro Mimaki Yutaka Sashida Tohru Yamakuni Yasushi Ohizumi Kohji Fukunaga | 2009 | Brain Research2009，，： | 1 |
| 4 | Role of MAP kinase in neurons显示文摘 | Kohji Fukunaga Eishichi Miyamoto | 1998 | Molecular Neurobiology1998，，1： | 1 |
| 5 | Role of MAP kinase in neurons显示文摘 | Kohji Fukunaga Eishichi Miyamoto | 1998 | Molecular Neurobiology1998，，1： | 1 |
| 6 | Role of Akt and ERK signaling in the neurogenesis following brain ischemia显示文摘 | Norifumi Shioda Han Feng Kohji Fukunaga | 2009 | Int Rev Neurobiol2009，85，： | 1 |
| 7 | BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination显示文摘Cerebellar ataxias are characterized by a progressive decline in motor coordination,but the specific output circuits and underlying pathological mechanism remain poorly understood.Through cell-type-specific manipulations,we discovered a novel GABAergic Purkinje cell(PC)circuit in the cerebellar IV/V lobe that projected to CaMKIIα+neurons in the fastigial nucleus(FN),which regulated sensorimotor coordination.Furthermore,transcriptomics profiling analysis revealed various cerebellar neuronal identities,and we validated that biorientation defective 1(BOD1)played an important role in the circuit of IV/V lobe to FN.BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs,accompany with ataxia behaviors.Instead,BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+neurons in the FN and ameliorated ataxia behaviors in L7-Cre;BOD1f/f mice.Together,these findings further suggest that specific regulation of the cerebellar IV/V lobePCs→FNCaMKIIα+circuit might provide neuromodulatory targets for the treatment of ataxia behaviors. | Xiu-Xiu Liu Xing-Hui Chen Zhi-Wei Zheng Qin Jiang Chen Li Lin Yang Xiang Chen Xing-Feng Mao Hao-Yang Yuan Li-Li Feng Quan Jiang Wei-Xing Shi Takuya Sasaki Kohji Fukunaga Zhong Chen Feng Han Ying-Mei Lu | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 1 |
| 8 | Microsphere embolism-induced endothelial nitric oxide synthase expression mediates disruption of the blood-brain barrier in rat brain 显示文摘 | Han Feng Shirasaki Yasufumi Fukunaga Kohji | 2006 | J Neurochem2006，99，1： | 1 |
| 9 | Pharmacological inhibition of FABP7 by MF 6 counteracts cerebellum dysfunction in an experimental multiple system atrophy mouse model显示文摘Multiple system atrophy(MSA)is a rare,fatal neurodegenerative disease characterized by the accumulation of misfolded asynuclein(asyn)in glial cells,leading to the formation of glial cytoplasmic inclusions(GCl).We previous found that glial fatty acidbinding protein 7(FABP7)played a crucial role in alpha-synuclein(aSyn)aggregation and toxicity in oligodendrocytes,inhibition of FABP7 by a specific inhibitor MF 6 reduced aSyn aggregation and enhanced cell viability in cultured cell lines and mouse oligodendrocyte progenitor cells.In this study we investigated whether MF 6 ameliorated aSyn-associated pathological processes in PLP-haSyn transgenic mice(PLP-aSyn mice),a wildly used MSA mouse model with overexpressing aSyn in oligodendroglia under the proteolipid protein(PLP)promoter.PLP-aSyn mice were orally administered MF6(0.1,1 mg·kg^(-1)·d^(-1))for 32 days starting from the age of 6 months.We showed that oral administration of MF 6 significantly improved motor function assessed in a pole test,and reduced aSyn aggregation levels in both cerebellum and basal ganglia of PLP-aSyn mice.Moreover,MF 6 administration decreased oxidative stress and inflammation levels,and improved myelin levels and Purkinje neuron morphology in the cerebellum.By using mouse brain tissue slices and aSyn aggregates-treated KG-1C cells,we demonstrated that MF 6 reduced aSyn propagation to Purkinje neurons and oligodendrocytes through regulating endocytosis.Overall,these results suggest that MF 6 improves cerebellar functions in MSA by inhibiting asyn aggregation and propagation.We conclude that MF 6 is a promising compound that warrants further development for the treatment of MSA. | An Cheng Wenbin Jia David I.Finkelstein Nadia Stefanova Haoyang Wang Takuya Sasaki Ichiro Kawahata Kohji Fukunaga | 2024 | Acta Pharmacologica Sinica2024，45，1： | 0 |
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