Zhen Yan
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View article: Ampk alpha2 T172 Activation Dictates Exercise Performance and Energy Transduction in Skeletal Muscle
Ampk alpha2 T172 Activation Dictates Exercise Performance and Energy Transduction in Skeletal Muscle Open
SUMMARY AMPK (5′-AMP-activated protein kinase) is an energetic sensor for metabolic regulation and integration. Here, we employed CRISPR/Cas9 to generate non-activatable Ampkα knock-in (KI) mice with mutation of threonine 172 phosphorylati…
View article: Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons
Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons Open
Hyperphosphorylation of Tau and the ensuing microtubule destabilization are linked to synaptic dysfunction in Alzheimer’s disease (AD). We find a marked increase of phosphorylated Tau (pTau) in cortical neurons differentiated from induced …
View article: Histone demethylase PHF2 regulates inflammatory genes in Alzheimer’s disease
Histone demethylase PHF2 regulates inflammatory genes in Alzheimer’s disease Open
A plethora of factors contribute to cognitive impairment in Alzheimer’s disease (AD), including neuroinflammation, synaptic dysfunction and gene alteration. In search of transcription factors controlling dysregulated genes in AD, we identi…
View article: Epigenomic Aberrations of Histone Methylation in Prefrontal Cortex of Humans with Mild Cognitive Impairment and Alzheimer’s Disease
Epigenomic Aberrations of Histone Methylation in Prefrontal Cortex of Humans with Mild Cognitive Impairment and Alzheimer’s Disease Open
Epigenetic mechanisms, particularly histone modifications at gene promoters, are crucial for controlling gene transcription. During the progression of neurodegenerative disorders, epigenomic aberrations may contribute to gene dysregulation…
View article: Synaptic Deficits in <i>Adnp‐</i>Mutant Mice Are Ameliorated by Histone Demethylase <scp>LSD1</scp> Inhibition
Synaptic Deficits in <i>Adnp‐</i>Mutant Mice Are Ameliorated by Histone Demethylase <span>LSD1</span> Inhibition Open
ADNP (Activity‐dependent neuroprotective protein) is a top‐ranking autism risk gene. Here we examined synaptic alterations in heterozygous mice carrying an autism mutation on Adnp C‐terminus ( Adnp mut ). We found that PFC pyramidal neuron…
View article: Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene <i>Smarcc2</i> and its Rescue by Histone Deacetylase Inhibition
Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene <i>Smarcc2</i> and its Rescue by Histone Deacetylase Inhibition Open
SMARCC2 , which encodes BAF170, a core subunit of chromatin remodeling BAF complex, is one of the top-ranking risk genes for autism spectrum disorder (ASD). However, the mechanisms linking SMARCC2 haploinsufficiency to ASD remain poorly un…
View article: CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model
CRISPR-based epigenetic editing of Gad1 improves synaptic inhibition and cognitive behavior in a Tauopathy mouse model Open
GABAergic signaling in the brain plays a key role in regulating synaptic transmission, neuronal excitability, and cognitive processes. Large-scale sequencing has revealed the diminished expression of GABA-related genes in Alzheimer's disea…
View article: Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice
Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice Open
Adverse experiences in early life can induce maladaptive responses to acute stress in later life. Chronic social isolation during adolescence is an early life adversity that can precipitate stress‐related psychiatric disorders. We found th…
View article: Distinct and Convergent Alterations of Entorhinal Cortical Circuits in Two Mouse Models for Alzheimer’s Disease and Related Disorders
Distinct and Convergent Alterations of Entorhinal Cortical Circuits in Two Mouse Models for Alzheimer’s Disease and Related Disorders Open
Background: The impairment of neural circuits controlling cognitive processes has been implicated in the pathophysiology of Alzheimer’s disease and related disorders (ADRD). However, it is largely unclear what circuits are specifically cha…
View article: Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy
Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy Open
The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting…
View article: An epigenetic mechanism of social isolation stress in adolescent female mice
An epigenetic mechanism of social isolation stress in adolescent female mice Open
View article: Longitudinal characterization of behavioral, morphological and transcriptomic changes in a tauopathy mouse model
Longitudinal characterization of behavioral, morphological and transcriptomic changes in a tauopathy mouse model Open
Neurodegenerative disorders, such as Alzheimer's disease (AD), have the gradual onset of neurobiological changes preceding clinical diagnosis by decades. To elucidate how brain dysfunction proceeds in neurodegenerative disorders, we perfor…
View article: PTBP2 attenuation facilitates fibroblast to neuron conversion by promoting alternative splicing of neuronal genes
PTBP2 attenuation facilitates fibroblast to neuron conversion by promoting alternative splicing of neuronal genes Open
The direct conversion of human skin fibroblasts to neurons has a low efficiency and unclear mechanism. Here, we show that the knockdown of PTBP2 significantly enhanced the transdifferentiation induced by ASCL1, MIR9/9∗-124, and …
View article: Epigenomic analysis of Alzheimer's disease brains reveals diminished CTCF binding on genes involved in synaptic organization
Epigenomic analysis of Alzheimer's disease brains reveals diminished CTCF binding on genes involved in synaptic organization Open
Epigenetic aberrations are suggested to play an important role in transcriptional alterations in Alzheimer's disease (AD). One of the key mechanisms of epigenetic regulation of gene expression is through the dynamic organization of chromat…
View article: Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits
Cholinergic neurons in the basal forebrain are involved in behavioral abnormalities associated with Cul3 deficiency: Role of prefrontal cortex projections in cognitive deficits Open
View article: Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model
Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model Open
Pleiotropic mechanisms have been implicated in Alzheimer’s disease (AD), including transcriptional dysregulation, protein misprocessing and synaptic dysfunction, but how they are mechanistically linked to induce cognitive deficits in AD is…
View article: Histone Deacetylase Inhibition Restores Behavioral and Synaptic Function in a Mouse Model of 16p11.2 Deletion
Histone Deacetylase Inhibition Restores Behavioral and Synaptic Function in a Mouse Model of 16p11.2 Deletion Open
Background Microdeletion of the human 16p11.2 gene locus confers risk for autism spectrum disorders and intellectual disability. How 16p11.2 deletion is linked to these neurodevelopmental disorders and whether there are treatment avenues f…
View article: Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells
Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells Open
View article: Epigenetics-based treatment strategies for Alzheimer’s disease
Epigenetics-based treatment strategies for Alzheimer’s disease Open
View article: A convergent mechanism of high risk factors <i>ADNP</i> and <i>POGZ</i> in neurodevelopmental disorders
A convergent mechanism of high risk factors <i>ADNP</i> and <i>POGZ</i> in neurodevelopmental disorders Open
ADNP and POGZ are two top-ranking risk factors for autism spectrum disorder and intellectual disability, but how they are linked to these neurodevelopmental disorders is largely unknown. Both ADNP and POGZ are chromatin regulators, which c…
View article: Molecular and cellular mechanisms for differential effects of chronic social isolation stress in males and females
Molecular and cellular mechanisms for differential effects of chronic social isolation stress in males and females Open
View article: Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models
Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models Open
View article: Selective impairment of circuits between prefrontal cortex glutamatergic neurons and basal forebrain cholinergic neurons in a tauopathy mouse model
Selective impairment of circuits between prefrontal cortex glutamatergic neurons and basal forebrain cholinergic neurons in a tauopathy mouse model Open
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder linked to cognitive decline. To understand how specific neuronal circuits are impaired in AD, we have used optogenetic and electrophysiological approaches to reveal the fun…
View article: AMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures
AMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures Open
Metabolism regulates neuronal activity and modulates the occurrence of epileptic seizures. Here, using two rodent models of absence epilepsy, we show that hypoglycaemia increases the occurrence of spike-wave seizures. We then show that sel…
View article: Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures
Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures Open
View article: Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and abnormal neural stem cell development
Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and abnormal neural stem cell development Open
View article: Rescue of histone hypoacetylation and social deficits by ketogenic diet in a Shank3 mouse model of autism
Rescue of histone hypoacetylation and social deficits by ketogenic diet in a Shank3 mouse model of autism Open
View article: Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model
Epigenetic treatment of behavioral and physiological deficits in a tauopathy mouse model Open
Epigenetic abnormality is implicated in neurodegenerative diseases associated with cognitive deficits, such as Alzheimer's disease (AD). A common feature of AD is the accumulation of neurofibrillary tangles composed of hyperphosphorylated …
View article: Working life job strain status and cognitive aging in Europe: A 12-year follow-up study
Working life job strain status and cognitive aging in Europe: A 12-year follow-up study Open
Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.
View article: Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription
Autism risk gene KMT5B deficiency in prefrontal cortex induces synaptic dysfunction and social deficits via alterations of DNA repair and gene transcription Open