A5055815966- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Neural dynamics and brain function
- Wnt/β-catenin signaling in development and cancer
- Tryptophan and brain disorders
- stochastic dynamics and bifurcation
- Palliative Care and End-of-Life Issues
- Gut microbiota and health
- Genomics and Rare Diseases
- Pluripotent Stem Cells Research
- Peptidase Inhibition and Analysis
- Clostridium difficile and Clostridium perfringens research
- biodegradable polymer synthesis and properties
- Healthcare Decision-Making and Restraints
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related gene regulation
- Prion Diseases and Protein Misfolding
University of California, Los Angeles
2010-2022
Instituto de Neurologia Y Neurocirugia
2021
University of Turin
2021
Smith-Kettlewell Eye Research Institute
2019
UCLA Health
1999-2017
Westwood College
1999
Discovery Institute
1997
Sanford Burnham Prebys Medical Discovery Institute
1997
A subset of individuals with familial amyotrophic lateral sclerosis (FALS) possesses dominantly inherited mutations in the gene that encodes copper-zinc superoxide dismutase (CuZnSOD). A4V and G93A, two mutant enzymes associated FALS, were shown to catalyze oxidation a model substrate (spin trap 5,5′-dimethyl-1-pyrroline N -oxide) by hydrogen peroxide at higher rate than seen wild-type enzyme. Catalysis this reaction G93A was more sensitive inhibition copper chelators diethyldithiocarbamate...
Abstract The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown be effective at generating motor neurons from human embryonic (hESCs), we found that once specified a neural lineage, iPS could differentiated form with similar efficiency as hESCs. Human iPS-derived appeared follow normal developmental progression associated neuron formation and possessed prototypical...
Abstract In amyotrophic lateral sclerosis, down‐regulation of the astrocyte‐specific glutamate excitatory amino acid transporter 2 is hypothesized to increase extracellular glutamate, thereby leading excitotoxic motor neuron death. The antibiotic ceftriaxone was recently reported induce and prolong survival mutant superoxide dismutase 1 transgenic mice. Here we show that also protects fibroblasts hippocampal cell line HT22, which are not sensitive excitotoxicity, against oxidative toxicity,...
The contribution of inflammation to neurodegenerative diseases is increasingly recognized, but the role in sporadic amyotrophic lateral sclerosis (sALS) not well understood and no animal model available. We used enzyme-linked immunosorbent assays (ELISAs) measure cytokine interleukin-17A (IL-17A) serum ALS patients (n = 32; 28 4 familial (fALS)) control subjects 14; 10 healthy with autoimmune disorders). IL-17A concentrations were 5767 ± 2700 pg/ml (mean SEM) sALS 937 927 fALS comparison 7 2...
Abstract We have previously shown higher-than-expected rates of schizophrenia in relatives patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate genetic ALS and using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, estimate correlation to be 14.3% (7.05–21.6; P =1 × 10 −4 ) polygenic risk scores explaining up 0.12% variance ( =8.4 −7 ). A...
The role of the human microbiome in health and disease is increasingly appreciated. We studied composition microbial communities present blood across 192 individuals, including healthy controls patients with three disorders affecting brain: schizophrenia, amyotrophic lateral sclerosis, bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate reads, we performed profiling transcripts detected whole blood. were able to detect a wide range bacterial archaeal phyla...
Background: Deposits of abnormally hyperphosphorylated tau are a hallmark several dementias, including Alzheimer disease (AD), and about 10% familial frontotemporal dementia (FTD) cases caused by mutations in the gene.As known kinase, GSK3B is promising candidate gene remaining FTD AD, for which have not been found.Objective: To examine promoter all 12 exons, surrounding intronic sequence, patients with FTD, aged healthy subjects to identify single-nucleotide polymorphisms associated...
Mutations in GDAP1 lead to recessively or dominantly inherited peripheral neuropathies (Charcot–Marie–Tooth disease, CMT), indicating that is essential for the viability of cells nervous system. contains domains characteristic glutathione-S-transferases (GSTs), located outer mitochondrial membrane and induces fragmentation mitochondria. We found upregulated neuronal HT22 selected resistance against oxidative stress. over-expression protected stress caused by depletion intracellular...
To determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial sporadic amyotrophic lateral sclerosis (SALS).Sixty participants with SALS from 10 centers were 1:1:1 to placebo, 300 mg/d, or 900 mg/d followed for 12 weeks. The primary endpoints tolerability. Secondary pharmacokinetic study plasma CSF, ALS Functional Rating Scale-Revised (ALSFRS-R) score, slow vital capacity (SVC), muscle cramp frequency severity.The only serious adverse event...
Abstract Background In a Phase 3 study, amyotrophic lateral sclerosis (ALS) patients experienced significantly less physical functional decline with 24‐week edaravone vs placebo, followed by open‐label treatment for an additional 24 weeks. Methods Outcome (the change in ALS Functional Rating Scale–Revised, ALSFRS‐R, from baseline) was projected placebo through 48 weeks and compared 48‐week or after switching placebo. Results A total of 123 received (65 edaravone‐edaravone; 58...
Advances in genomics and proteomics permit rapid identification of disease-relevant genes proteins. Challenges include biological differences between animal models human diseases, high discordance DNA protein expression data a lack experimental to study complex diseases. To overcome some these limitations, we developed an integrative approach using models, postmortem material combination high-throughput microarray methods identify novel molecular markers amyotrophic lateral sclerosis (ALS)....
Accumulation of neurotoxic hyperphosphorylated TAU protein is a major pathological hallmark Alzheimer disease and other neurodegenerative dementias collectively called tauopathies. Puromycin-sensitive aminopeptidase (PSA/NPEPPS) novel modifier TAU-induced neurodegeneration with neuroprotective effects via direct proteolysis protein. Here, to examine the PSA/NPEPPS overexpression in vivo mammalian system, we generated crossed BAC-PSA/NPEPPS transgenic mice TAUP301L mouse model...
More than 90% of amyotrophic lateral sclerosis (ALS) patients have muscle cramps, but evidence-based treatments not been available.
Background Edaravone slowed the rate of functional decline in subjects with amyotrophic lateral sclerosis (ALS) phase 3 study MCI186-19 (Study 19). One Study 19 inclusion criteria was forced vital capacity (FVC) ≥80% predicted (≥80%p). Therefore, provided no information on edaravone efficacy FVC <80%p. In 19, 24-week, double-blind treatment followed by open-label where all received edaravone. At 24 weeks, some had <80%p (FVC <80%p). This allowed for post-hoc assessment effects...
SUMMARY Human embryonic stem cell (hESC)-derived neurons have the potential to model neurodegenerative disorders. Here, we demonstrate expression of a mutant gene, superoxide dismutase 1(SOD1), linked familial amyotrophic lateral sclerosis (ALS) in hESC-derived motor neurons. Green fluorescent protein (GFP) under control HB9 enhancer was used identify SOD1-transfected that express human wild-type SOD1 or one three different mutants (G93A, A4V and I113T) SOD1. Neurons transfected with...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons degenerate, resulting muscle atrophy, paralysis, and fatality. Studies using mouse models of ALS indicate protracted period development with progressive neuron pathology, evident as early embryonic postnatal stages. Key missing information includes concomitant alterations the sensorimotor circuit essential for normal function neuromuscular system. Leveraging unique brainstem circuitry, we show vitro...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron disease with presently no cure. Motoneuron (MN) hyperexcitability commonly observed in ALS and suggested to be precursor for excitotoxic cell death. However, it unknown whether also occurs MNs that are resistant degeneration. Second, unclear all the within homogeneous motor pools would present similar susceptibility excitability changes since high-threshold innervating fast fatigable muscle fibers selectively...
Study Design. A case report. Objectives. To document the rare condition of staphylococcal osteomyelitis odontoid process and to increase knowledge about clinical characteristics favorable outcome if patients are managed appropriately. Summary Background Data. Osteomyelitis caused by Staphylococcus aureus is a disease. handful cases have been reported within last 30 years. Destructive peg involvement most commonly associated with rheumatoid disease, which has distinct course compared that...