A5034227227- GDF15 and Related Biomarkers
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Nutrition and Health in Aging
- Macrophage Migration Inhibitory Factor
- Cholinesterase and Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Amyotrophic Lateral Sclerosis Research
- MicroRNA in disease regulation
- Prion Diseases and Protein Misfolding
- Circular RNAs in diseases
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Neurogenetic and Muscular Disorders Research
- Nerve injury and regeneration
- Protein Hydrolysis and Bioactive Peptides
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Apelin-related biomedical research
- Neurogenesis and neuroplasticity mechanisms
- Retinoids in leukemia and cellular processes
Sophia University
2014-2024
Simon Fraser University
2010-2013
Georgetown University
2007-2012
Georgetown University Medical Center
2008-2012
Keio University
2000-2008
Keio University Hospital
2000-2005
University of California, Los Angeles
2003
The University of Tokyo
2003
Mattel Children's Hospital
2003
Nagoya University
2001
Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes short polypeptide and abolishes death of neuronal cells caused by multiple different types familial Alzheimer's disease genes Aβ amyloid, without effect on Q79 or superoxide dismutase-1 mutants. Transfected HN cDNA was transcribed to the corresponding then secreted into cultured medium. The rescue action clearly depended primary structure HN. This would serve as molecular clue for...
Insulin-like growth factor-binding protein-3 (IGFBP-3) regulates IGF bioactivity and also independently modulates cell survival. By using a yeast two-hybrid screen to identify IGFBP-3-interacting proteins, we cloned humanin (HN) as an IGFBP-3-binding partner. HN is 24-aa peptide that has been shown specifically inhibit neuronal death induced by familial Alzheimer's disease mutant genes amyloid-β (Aβ). The physical interaction of with IGFBP-3 was determined be high affinity specificity...
A novel factor, termed Humanin (HN), antagonizes against neurotoxicity by various types of familial Alzheimer's disease (AD) genes [V642I and K595N/M596L (NL) mutants amyloid precursor protein (APP), M146L-presenilin (PS) 1, N141I-PS2] Abeta1-43 with clear action specificity ineffective on polyglutamine repeat Q79 or superoxide dismutase 1 mutants. Here we report that HN can also inhibit other AD-relevant insults: AD (A617G-APP, L648P-APP, A246E-PS1, L286V-PS1, C410Y-PS1, H163R-PS1), APP...
Brain atrophy caused by neuronal loss is a prominent pathological feature of Alzheimer's disease (AD). Amyloid beta (Abeta), the major component senile plaques, considered to play central role in cell death. In addition removal toxic Abeta, direct suppression an essential part AD treatment; however, no such neuroprotective therapies have been developed. Excess amount Abeta evokes multiple cytotoxic mechanisms, involving increase intracellular Ca(2+) level, oxidative stress, and...
Several epidemiological and preclinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), reduce the risk of Alzheimer's disease (AD) can lower β-amyloid (Aβ) production neuroinflammation. However, follow-up clinical trials, mostly using selective (COX)-2 inhibitors, failed to show any beneficial effect in AD patients with mild severe cognitive deficits. Recent data indicated COX-1, classically viewed as homeostatic isoform, is localized...
Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries. In addition to known interacting proteins containing phosphotyrosine-interaction-domain (PID)-Fe65, Fe65L, Fe65L2, X11, mDab1, identified, as novel APP-interacting molecule, PID-containing isoform of JNK-interacting protein-1 (JIP-1b) its homolog IB1, the established scaffold JNK. The APP amino acids Tyr(682), Asn(684), Tyr(687) in...
Abstract Humanin (HN) is a newly identified neuroprotective peptide that specifically suppresses Alzheimer's disease (AD)‐related neurotoxicity. HN has been detected in the human AD brain as well mouse testis and colon by immunoblot immunohistochemical analyses. By means of yeast two‐hybrid screening, we TRIM11 novel HN‐interacting protein. TRIM11, which member protein family containing tripartite motif (TRIM), composed RING finger domain, putative E3 ubiquitin ligase, B‐box coiled‐coil...
Abstract Humanin (HN) is a 24‐amino acid peptide that protects neuronal cells from death caused by Alzheimer's disease (AD)‐related genes and amyloid‐β (Aβ). Multiple studies have revealed its biochemical neuroprotective characteristics in vitro; however, little has been known regarding whether HN effective vivo AD model systems. We examined the effect of S14G‐HN, 1,000‐fold more potent derivative vitro, on amnesia induced Aβ25–35 mice. The Y‐maze test at least 50 pmol S14G‐HN...
Humanin (HN), a 24-residue peptide, was identified as novel neuroprotective factor and shows anti-cell death activity against wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection S14G-HN, highly potent HN derivative, into brain ameliorated memory loss an Abeta-injection mouse model. To fully understand HN's functions under AD-associated pathological conditions, we examined effect...
Abstract Amyloid precursor protein (APP), the of Aβ, has been shown to function as a cell surface receptor that mediates neuronal death by anti‐APP antibody. The c‐Jun N‐terminal kinase (JNK) can mediate various neurotoxic signals, including Aβ neurotoxicity. However, relationship APP‐mediated neurotoxicity JNK is not clear, partly because APP cytotoxicity independent. Here we examined whether involved in and found that: (i) antibody‐bound was inhibited dominant‐negative JNK, JIP‐1b...
Mutation of the ALS2 gene encoding alsin is linked to onset autosomal recessive motor neuron diseases, including juvenile-onset amyotrophic lateral sclerosis (ALS). Alsin long form (LF) belongs family guanine nucleotide exchanging factor (GEF) for small GTPases. Expression LF, but not short form, protected neuronal cells from toxicity induced by mutants Cu/Zn-superoxide dismutase (SOD1) gene, which cause dominant ALS. In contrast, expression did suppress neurotoxicity other neurodegenerative...
Abstract Neuronal pathology of the brain with Alzheimer's disease (AD) is characterized by numerous depositions amyloid‐β peptides (Aβ). Aβ binding to 75‐kDa neurotrophin receptor (p75NTR) causes neuronal cell death. Here we report that death in hybrid cells transfected p75NTR, but not nontransfected cells, and p75NTR L401K cannot mediate neurotoxicity. We analyzed cytotoxic pathway transfecting pertussis toxin (PTX)‐resistant G protein α subunits presence PTX identified Gα o , i proteins...
The epsilon4 genotype of apolipoprotein E (apoE4) is the most established predisposing factor in Alzheimer's disease (AD); however, it remains unclear how apoE4 contributes to pathophysiology. Here, we report that protein (ApoE4) evokes apoptosis neuronal cells through low-density lipoprotein receptor-related (LRP) and heterotrimeric GTPases. We examined neuron/neuroblastoma hybrid F11 found these were killed by 30 microg/ml ApoE4, but not ApoE3. ApoE4-induced death occurred with typical...
Aquaporin-4 (AQP4) has been suggested to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), which may due modulation neuroinflammation or impairment interstitial fluid bulk flow system central nervous system. Here, we show an age-dependent several behavioral outcomes 5xFAD AQP4 null mice. Twenty-four-hour video recordings and computational analyses their movement revealed that nighttime motion AQP4-deficient mice was progressively reduced...
It has been found that insulin-like growth factor I (IGF-I) exerts cytoprotection against Abeta amyloid-induced neuronal cell death. Deposits of amyloid are one the pathological hallmarks Alzheimer's disease (AD). Here, we examined whether IGF-I protective activity death induced by a familial AD (FAD)-linked mutant precursor protein (APP), and protected cells from toxicity FAD-associated V642I APP in multiple systems. IGFBP-3 blocked this action IGF-I, but not des(1-3)IGF-I, which was as...
The biological function of full-length amyloid-β protein precursor (AβPP), the Aβ, is not fully understood. Multiple laboratories have reported that antibody binding to cell surface AβPP causes neuronal death. Here we examined whether induced dimerization cytoplasmic domain (AβPP<sub>CD</sub>) triggers In neurohybrid cells expressing fusion constructs epidermal growth factor (EGF) receptor with AβPP<sub>CD</sub> (EGFR/AβPP hybrids), EGF drastically enhanced death in a manner sensitive...
Abstract The 24‐residue peptide Humanin (HN), containing two Ser residues at positions 7 and 14, protects neuronal cells from insults of various Alzheimer's disease (AD) genes Aβ. It was not known why the rescue function (S14G)HN is more potent than HN by to three orders magnitude. Investigating possibility that post‐translational modification Ser14 might play a role, we found with d ‐Ser position 14 exerts neuroprotection potently magnitude, whereas ‐Ser7 substitution does affect HN. On...