Xiangyou Hu, Ph.D.Assistant Professor, Neuroscience
|B.S.||Anhui Medical University||Medicine|
|M.S.||Department of Anatomy, Henan Medical University||Neurobiology|
|Ph.D.||Department of Neurobiology, School of Life Sciences, University of Science and Technology of China||Neurobiology|
|Postdoctoral||Cleveland Clinic Lerner Research Institute||Postdoctoral Research Fellow, Department of Neurosciences|
|Name of Award/Honor||Awarding Organization|
|William E. Lower Award for Basic Science Research||Cleveland Clinic Lerner Research Institute|
|Innovator Award for identification of RTN3 aggregates in Alzheimer’s brains||Cleveland Clinic|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Alzheimer's Association International Society||Professional/Scientific Organization||Member||External||International||2020|
|Society for Neuroscience||Professional/Scientific Organization||Member||External||National||2015|
Alzheimer’s disease (AD), the most common cause of age-related dementia, is a debilitating neurodegenerative disease that leads to progressive memory loss, cognitive impairment, and ultimately death. The β-site APP cleaving enzyme 1 (BACE1) is a major drug target for AD treatment because BACE1-mediated cleavage of APP is the first step in the generation of pathogenic amyloid-β peptides. My lab focuses on investigation of BACE1 biological functions and the roles of BACE1 in the pathogenesis of Alzheimer’s disease using both conditional and constitutional BACE1 knockout mice.
Considering the fact of epileptiform activity and sleep disorders occurs more frequently in AD patients, our one project is examining whether BACE1 inhibition impacts seizure activity and sleep disorders in AD mice and further characterize the correlation of plaque loading with epileptiform spikes, NREM and REM sleep times in AD mice models.
Lower urinary tract dysfunction (LUTD) is another most common symptoms in AD. However, the pathophysiological link between AD and LUTD is not well defined. We have another project focusing on investigation of bladder pathology, nerve innervation, neurotransmitters and the receptors distribution, and muscle-specific responses in AD bladders.
Accepting Lab Rotation Students: Summer 2023, Fall 2023, and Spring 2024
Postnatal neuronal Bace1 deletion impairs neuroblast and oligodendrocyte maturation.
Human molecular genetics 2022 Nov;
Targeted BACE-1 inhibition in microglia enhances amyloid clearance and improved cognitive performance.
Science advances 2022 Jul;8(29):eabo3610
Alzheimer's disease amyloidogenesis is linked to altered lower urinary tract physiology.
Neurourology and urodynamics 2022 May;
BACE1 controls synaptic function through modulating release of synaptic vesicles.
Molecular psychiatry 2021 Jun;
Activated CX3CL1/Smad2 signals prevent neuronal loss and Alzheimer's tau pathology-mediated cognitive dysfunction.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2019 Dec;
Dystrophic neurites labelled by pre-autophagosomal proteins in Alzheimer's brains.
Molecular psychiatry 2019 Sep;24(9):1247
The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer's amyloid pathology.
The Journal of experimental medicine 2019 Jun;
BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions.
The Journal of experimental medicine 2018 Mar;215(3):927-940
BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus.
Stem cell reports 2017 Jul;9(1):217-230
BACE1 regulates the proliferation and cellular functions of Schwann cells.
Glia 2017 May;65(5):712-726
Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.
Molecular psychiatry 2016 Sep;21(9):1263-71
Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.
Journal of neurochemistry 2016 Jan;136(2):234-49
Axonal and Schwann cell BACE1 is equally required for remyelination of peripheral nerves.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2015 Mar;35(9):3806-14
Impact of RTN3 deficiency on expression of BACE1 and amyloid deposition.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2014 Oct;34(42):13954-62
Reversible overexpression of bace1-cleaved neuregulin-1 N-terminal fragment induces schizophrenia-like phenotypes in mice.
Biological psychiatry 2014 Jul;76(2):120-7
Increased expression of reticulon 3 in neurons leads to reduced axonal transport of β site amyloid precursor protein-cleaving enzyme 1.
The Journal of biological chemistry 2013 Oct;288(42):30236-45
BACE1 regulates hippocampal astrogenesis via the Jagged1-Notch pathway.
Cell reports 2013 Jul;4(1):40-9
Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2013 May;27(5):1868-73
Preventing formation of reticulon 3 immunoreactive dystrophic neurites improves cognitive function in mice.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2013 Feb;33(7):3059-66
Interaction between amyloid precursor protein and Nogo receptors regulates amyloid deposition.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2011 Sep;25(9):3146-56
Cleavage of neuregulin-1 by BACE1 or ADAM10 protein produces differential effects on myelination.
The Journal of biological chemistry 2011 Jul;286(27):23967-74
RTN/Nogo in forming Alzheimer's neuritic plaques.
Neuroscience and biobehavioral reviews 2010 Jul;34(8):1201-6
BACE1 deficiency causes altered neuronal activity and neurodegeneration.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2010 Jun;30(26):8819-29
Reduced amyloid deposition in mice overexpressing RTN3 is adversely affected by preformed dystrophic neurites.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2009 Jul;29(29):9163-73
The occurrence of aging-dependent reticulon 3 immunoreactive dystrophic neurites decreases cognitive function.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2009 Apr;29(16):5108-15
Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2008 Aug;22(8):2970-80
Transgenic mice overexpressing reticulon 3 develop neuritic abnormalities.
The EMBO journal 2007 Jun;26(11):2755-67
Bace1 modulates myelination in the central and peripheral nervous system.
Nature neuroscience 2006 Dec;9(12):1520-5
Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins.
Journal of molecular biology 2006 Oct;363(3):625-34
The expression of calcium/calmodulin-dependent protein kinase II-alpha in the hippocampus of patients with Alzheimer's disease and its links with AD-related pathology.
Brain research 2005 Jan;1031(1):101-8
Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation.
Nature medicine 2004 Sep;10(9):959-65
Regional alteration of synapsin I in the hippocampal formation of Alzheimer's disease patients.
Acta neuropathologica 2004 Mar;107(3):209-15
Estrogen receptor alpha-immunoreactive astrocytes are increased in the hippocampus in Alzheimer's disease.
Experimental neurology 2003 Oct;183(2):482-8
Decreased estrogen receptor-alpha expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients.
Acta neuropathologica 2003 Sep;106(3):213-20
Neurotensin expressing neurons developed earlier than vasoactive intestinal polypeptide and vasopressin expressing neurons in the human suprachiasmatic nucleus.
Neuroscience letters 2003 Jan;335(3):175-8
Increased p75(NTR) expression in hippocampal neurons containing hyperphosphorylated tau in Alzheimer patients.
Experimental neurology 2002 Nov;178(1):104-11
Reticulon proteins: emerging players in neurodegenerative diseases.
Cellular and molecular life sciences : CMLS 2006 Apr;63(7-8):877-89
|Title or Abstract||Type||Sponsor/Event||Date/Year||Location|
|BACE1 deletion in the adult reverses epileptiform activity and sleep-wake disturbances in AD mice models||Talk||UConn Health Department of Neuroscience||2022||UConn Health|
|Deletion of neuronal BACE1 causes mice memory deficits.||Talk||Alzheimer’s Association International Conference||2020||Amsterdam, Netherlands|
|BACE1 deletion in the adult mouse reverses preformed amyloid deposition and improves cognitive functions.||Talk||University of Science and Technology of Chin||2019||China|
|Accumulation of lysosomal vesicles and ferritin in dystrophic neurites and their selective degradation in Alzheimer’s disease mice brain.||Talk||Society for Neuroscience Annual Meeting||2019||Chicago, IL|
|BACE1 regulates Schwann cell proliferation in the sciatic nerve.||Talk||Anhui Medical University||2018||China|
|BACE1 deletion removing pre-formed amyloid plaques in 5xFAD mice.||Talk||UConn Health Department of Neuroscience||2018||Farmington, CT|
|Exploring BACE1 physiological function in BACE1-null mice.||Talk||University of Science and Technology of China School of Life Sciences||2016||China|
|BACE1 regulates hippocampal astrogenesis via the Jagged1-Notch pathway.||Talk||Anhui Medical University||2015||China|
|Schwann cell BACE1 is required for remyelination of peripheral nerves.||Talk||International Conference on Alzheimer's and Parkinson's Diseases||2015||Nice, France|