A5015480000- Nerve injury and regeneration
- Endoplasmic Reticulum Stress and Disease
- Cephalopods and Marine Biology
- Planarian Biology and Electrostimulation
- Cell death mechanisms and regulation
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Bioactive Compounds and Antitumor Agents
- Toxin Mechanisms and Immunotoxins
- Hereditary Neurological Disorders
- Lipid metabolism and biosynthesis
- Coenzyme Q10 studies and effects
- Nuclear Receptors and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Melanoma and MAPK Pathways
- Immune Response and Inflammation
- Signaling Pathways in Disease
China Agricultural University
2021-2024
Chinese Institute for Brain Research
2024
National Institute of Biological Sciences, Beijing
2016-2019
Tsinghua University
2018-2019
Beijing Institute of Technology
2011-2017
University of Saskatchewan
2013-2015
Institute of Cell Biology and Neurobiology
2013-2015
Cameco (Canada)
2013-2014
Macrophage recruitment to the injured nerve initiates a cascade of events, including myelin debris clearance and trophic factor secretion, which contribute proper tissue repair. However, mechanism macrophage is still unclear. Here, by comparing wild-type with Mlkl−/− Sarm1−/− mice, two mouse strains impaired after peripheral injury, we identify interleukin-17B (IL-17B) as key regulator recruitment. Schwann-cell-secreted IL-17B acts in an autocrine manner binds IL-17 receptor B promote...
Significance Peripheral nerve injury often occurs at axonal sites remote from the neuronal cell bodies. Information about these injuries must be accurately relayed back to body as part of reprogramming that transition neuron a regenerating state. We provide new insights into how endoplasmic reticulum (ER) proximal site generates critical regeneration signal in sensory neurons. This involves injury-triggered activation and synthesis an intraaxonal, ER transmembrane transcription factor,...
We recently revealed that the axon endoplasmic reticulum resident transcription factor Luman/CREB3 (herein called Luman) serves as a unique retrograde injury signal in regulation of intrinsic elongating form sensory regeneration. Here, evidence supports Luman contributes to axonal regeneration through unfolded protein response (UPR) and cholesterol biosynthesis adult rat neurons. One day sciatic nerve crush triggered robust increase UPR-associated mRNA expression both neuronal cell bodies...
Significance Myelin sheaths insulate the neuronal axons and speed transmission of electrical impulses. The demyelination process occurs in many human diseases, including multiple sclerosis (MS). Using mouse models MS, we demonstrate this study role MLKL, a protein known to function form regulated necrosis (necroptosis), facilitating necroptosis-independent manner central nervous system. An RIP1 kinase inhibitor was shown block progression MS an immune-induced model, it does so at stage after...
A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis inhibitors. These represent the first class inhibitors that function through stabilizing mitochondrial respiratory complex II. Starting from a phenotypic screen hit with micromolar activity, we optimized cellular inhibition activity to picomolar level (compound 42, also named TC9-305). The therapeutic potential these new further demonstrated by their neuroprotective effect on an ischemic animal model.
Amyloid β protein (Aβ) is the primary component of senile plaques in Alzheimer’s disease brains and its aggregate form neurotoxic. Aβ generated through proteolysis β-amyloid precursor (APP) by two proteases: β-secretase γ-secretase. BACE1, vivo key rate-limiting enzyme that initiates formation Aβ, an attractive drug target for AD therapy. Our previous study demonstrated BACE1 ubiquitinated degradation effect on APP cleaving process are mediated ubiquitin-proteasome pathway. However, specific...
Cells respond to perturbations in the microenvironment of endoplasmic reticulum (ER), and overloading its capacity process secretory membrane-associate proteins, by activating Unfolded Protein Response (UPR). Genes that mediate UPR are regulated three basic leucine-zipper (bLZip) motif-containing transcription factors – Xbp1s, ATF4 ATF6. A failure achieve homeostasis continued stimulation leads apoptosis. Mechanisms must therefore exist turn off if it successfully restores normalcy. The...
Apoptosis activation by cytochrome c release from mitochondria to cytosol is a normal cellular response mitochondrial damage. Using apoptosis assay, we have found small-molecule inhibitors that protect cells Previously, reported the discovery of small molecule, Compound A, which blocks dopaminergic neuron death in rat model Parkinson’s disease through targeting succinate dehydrogenase subunit B (SDHB) complex II integrity respiratory chain. Here, report R6, saves via mammalian target...
SignificanceDiabetic neuropathy is a commonly occurring complication of diabetes that affects hundreds millions patients worldwide. Patients suffering from diabetic experience abnormal sensations and have damage in their peripheral nerve axons as well myelin, tightly packed Schwann cell sheath wraps around to provide insulation increases electrical conductivity along the fibers. The molecular events underlying myelin are largely unknown, there no efficacious treatment for disease. current...
Peripheral nerve injury results in dramatic upregulation pituitary adenylate cyclase activating polypeptide (PACAP) expression adult rat dorsal root ganglia and spinal motor neurons mirroring that described for the neurotrophin brain derived neurotrophic factor (BDNF). Thus, we posited injury-associated alterations BDNF regulate changes PACAP observed injured neurons. The role of endogenous induction and/or maintenance mRNA sensory was examined by intrathecally infusing or intraperitoneally...
Activation of the nerve growth factor (NGF) receptor trkA and tissue acidosis are critically linked to inflammation-associated nociceptor sensitization. This study explored how increased acidity is sensory neuron sensitization NGF. Adult Wistar rat primary neurons grown at physiological pH 7.4, then either kept 7.4 or challenged for 30 min in 6.5 medium, provided a model acidosis. Nonpermeabilizing immunofluorescence revealed significant increase mobilization plasma membrane from...
Adrenoleukodystrophy protein (ALDP) is responsible for the transport of very-long-chain fatty acids (VLCFAs) and corresponding CoA-esters across peroxisomal membrane. Dysfunction ALDP leads to metabolic disorder exemplified by X-linked adrenoleukodystrophy (ALD). Hundreds ALD-causing mutations have been identified on ALDP. However, pathogenic mechanisms these are restricted clinical description due limited structural biochemical characterization. Here we report cryo-electron microscopy...
Spatial localization ability is crucial for free-living animals to fit the environment. As shown by previous studies, planarians can be conditioned discriminate directions. However, due their simplicity and primitiveness, they had never been considered have true spatial retrieve locations of objects places in Here, we introduce a light maze training paradigm demonstrate that planarian worm navigate former recognized place from start point, even if transferred into newly produced maze. This...
Abstract Spatial localization ability is crucial for free-living animals to fit the environment. As shown by previous studies, planarians can be conditioned discriminate directions. However, due their simplicity and primitiveness, they had never been considered have true spatial retrieve locations of objects places in Here, we introduce a light maze training paradigm demonstrate that planarian worm navigate former recognized place from start point, even if transferred into newly produced...
Abstract Planarians, the first kind of animal to have evolved a brain structure 1 yet has not visual sense, was demonstrated capability spatial learning in last several decades 2 , but what does navigation planarians depends on is still unknown. Here, we provide an objective, strictly variable-controlled planarian training method using 3D printing techniques 3 fabricated mazes. Then use modifications mazes demonstrate paradigm that worms can memorize location darkened surrounding through...