A5079629636- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- 14-3-3 protein interactions
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Axon Guidance and Neuronal Signaling
- Tryptophan and brain disorders
- Adipose Tissue and Metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
Harvard University
2014-2023
Boston VA Research Institute
2022
Yankton Rural Area Health Education Center
2013
Harvard University Press
2005-2011
Boston Children's Hospital
1996-2006
Children's Hospital
2003
National Institutes of Health
1999
Brigham and Women's Hospital
1999
Dana-Farber Cancer Institute
1993
Beth Israel Deaconess Hospital
1991
The amyloid β protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role unknown. In culture, was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic mature higher concentrations. differentiated neurons, caused dendritic axonal retraction followed by neuronal death. A portion (amino acids 25 35) mediated both trophic toxic effects homologous tachykinin neuropeptide family. were mimicked antagonists completely reversed...
beta-Amyloid (beta A) is normally produced as a nontoxic soluble peptide. In Alzheimer disease, beta A aggregates and accumulates in the brain inert diffuse plaques or compact associated with neurodegenerative changes. To determine relationship of neurotoxicity to physical state A, we created (i) nonamyloidogenic amorphous [amorphous (Am-beta A)] analogous (ii) amyloidogenic fibrils [fibrillar (Fib-beta plaques. primary rat hippocampal culture, Fib-beta was neurotoxic, whereas Am-beta not...
Amyloid deposition in senile plaques and the cerebral vasculature is a marker of Alzheimer's disease. Whether amyloid itself contributes to neurodegenerative process or simply by-product that unknown. Pheochromocytoma (PC12) fibroblast (NIH 3T3) cell lines were transfected with portions gene for human precursor protein. Stable PC12 transfectants expressing specific amyloid-containing fragment protein gradually degenerated when induced differentiate into neuronal cells nerve growth factor....
Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence-associated secretory phenotype (SASP), pro-inflammatory response linked to promotion aging. We have identified transcription factor GATA4 as SASP regulator. stabilized in cells undergoing required for SASP. Normally, degraded p62-mediated selective autophagy, but this regulation suppressed during senescence, thereby stabilizing GATA4....
Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to autophagy dysfunction are still not clear. Based on results genome-wide screen, we show reactive oxygen species (ROS) serve as common mediators upstream activation type III PI3 kinase, which is critical initiation autophagy. Furthermore, ROS play an function induction kinase and response...
The cellular mechanism underlying the generation of beta-amyloid in Alzheimer disease and its relationship to normal metabolism amyloid precursor protein are unknown. In this report, we show that 3- 4-kDa peptides derived from normally secreted. Epitope mapping radiolabel sequence analysis suggest peptide is closely related full-length 3-kDa species a heterogeneous set truncated at N terminus. secreted parallel with protein. Inhibitors Golgi processing inhibit secretion peptides, whereas...
Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark Alzheimer disease (AD). Focal deposition beta amyloid adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons neurites. Chronic induction Alz-50 antigen appeared around focal cortical deposits amyloid. Immunoblot analysis showed that induced Alz-50-immunoreactive proteins were very similar to human from patients with AD. The neuropeptide substance P...