Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling network...The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.展开更多
There is much recent interest in the role of the anti-inflammatory molecules and their receptors in the normal brain and in neurological disorders.The formyl peptide receptor(FPR)subfamily of G protein-coupled recepto...There is much recent interest in the role of the anti-inflammatory molecules and their receptors in the normal brain and in neurological disorders.The formyl peptide receptor(FPR)subfamily of G protein-coupled receptors play important roles in these processes.Binding to specific peptides triggers activation of FPRs,leading to signalling events that regulate inflammatory responses.One member of this subfamily of receptors is FPR2,also known as ALX(the lipoxin A4(LXA4)receptor).FPR2 is specifically activated by LXA4 and resolvin D1(RvD1)(Pirault and B.ck,2018).展开更多
Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed...Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed by lysine methyltransferase G9a,which functions as a heteromeric complex with G9a-like protein(GLP).G9a/GLP has other non-histone substrates,including itself.G9a/GLP is implicated in regulating synaptic plasticity,learning and memory[2,3].展开更多
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
基金the Singapore Ministry of Education(T1-2015 Apr-03)the National University of SingaporeInstitute for Health Innovation and Technology to JJEC.
文摘The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.
文摘There is much recent interest in the role of the anti-inflammatory molecules and their receptors in the normal brain and in neurological disorders.The formyl peptide receptor(FPR)subfamily of G protein-coupled receptors play important roles in these processes.Binding to specific peptides triggers activation of FPRs,leading to signalling events that regulate inflammatory responses.One member of this subfamily of receptors is FPR2,also known as ALX(the lipoxin A4(LXA4)receptor).FPR2 is specifically activated by LXA4 and resolvin D1(RvD1)(Pirault and B.ck,2018).
基金This study was performed in accordance with the ethical review and received approval from the Institutional Animal Care and Use Committee(IACUC)of the National University of Singapore(IACUC protocol number:R16-0135).
文摘Histone H3 lysine 9 di-methylation(H3K9me2)is an epigenetic repressive histone modification that was found at aberrant states in Alzheimer’s disease(AD)patient samples[1].The addition of H3K9me2/3 is mainly catalyzed by lysine methyltransferase G9a,which functions as a heteromeric complex with G9a-like protein(GLP).G9a/GLP has other non-histone substrates,including itself.G9a/GLP is implicated in regulating synaptic plasticity,learning and memory[2,3].
