A5080468636- Viral Infections and Immunology Research
- Amyotrophic Lateral Sclerosis Research
- Animal Virus Infections Studies
- Neurogenetic and Muscular Disorders Research
- Plant Virus Research Studies
- Herpesvirus Infections and Treatments
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Viral gastroenteritis research and epidemiology
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Polyomavirus and related diseases
- Monoclonal and Polyclonal Antibodies Research
- Virology and Viral Diseases
- Alzheimer's disease research and treatments
- Virus-based gene therapy research
- T-cell and Retrovirus Studies
- Peripheral Neuropathies and Disorders
- Hereditary Neurological Disorders
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- RNA and protein synthesis mechanisms
- Multiple Sclerosis Research Studies
University of Chicago
2014-2024
University of Chicago Medical Center
2012-2023
Neuroscience Institute
2023
Centre Hospitalier de l’Université de Montréal
2020
McGill University
2020
Chicago Neuropsychology Group
2019
University of Miami
2017-2019
Erasmus Hospital
2017-2019
Université Libre de Bruxelles
2017-2019
University of Utah
1991-2019
Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause approximately 20% of cases familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism mutant SOD-induced neuronal degeneration by expressing wild-type and SODs cells means infection with replication-deficient recombinant adenoviruses. Expression two FALS-related (A4V V148G) caused death differentiated PC12 cells, superior cervical ganglion neurons, hippocampal pyramidal neurons. Cell included many features typical...
The development of new weakness, fatigue, and pain decades after acute paralytic poliomyelitis is a recognized syndrome. We conducted controlled study this syndrome by analyzing clinical, electromyographic, muscle-biopsy features in 18 patients with history poliomyelitis--13 reporting 1 to 20 years weakness 5 without symptoms. also reported muscle atrophy (9 13) fatigue (10 13), symptoms not the controls. age at time poliomyelitis, severity residual disability, number since were comparable...
We conducted this study to better inform amyotrophic lateral sclerosis (ALS) patients about home ventilation and assist them in decision-making. gathered data on the prevalence of ALS northern Illinois percentage who chose it, we asked identified subjects, their families, physicians for attitudes toward ventilation. Fewer than 10% had chosen ventilation, fewer 5% were still it. Seventeen (90%) glad have would choose it again. Family caregivers reported major burdens, only half themselves....
Approximately 10% of patients with amyotrophic lateral sclerosis (ALS) have familial ALS (FALS), and 20% FALS are caused by mutations superoxide dismutase type 1 (MTSOD1). The fact that some MTSOD1s cause full activity (e.g. G37R) others no G85R) suggests MTSOD1 causes due to toxicity the protein rather than a loss in enzymatic function. Compelling data demonstrated motor neuron (MN) degeneration can result from non-cell autonomous effect MTSOD1. In order clarify role astrocytes FALS, we...
Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) activates unfolded protein response (UPR), suggesting ER stress involved in pathogenesis FALS. We used a genetic approach investigate role UPR crossed G85RSOD1 transgenic mice with pancreatic kinase haploinsufficient (PERK+/−) obtain G85R/PERK+/−...
Varied stresses to cells can lead a repression in translation by triggering phosphorylation of eukaryotic initiator factor 2α (eIF2α), which is central process known as the integrated stress response (ISR). PKR-like ER-localized eIF2 kinase (PERK), one kinases that phosphorylates eIF2α and coordinates ISR, activated occurring from accumulation misfolded or unfolded proteins endoplasmic reticulum (ER). Mutant Cu/Zn superoxide dismutase (mtSOD1) thought cause familial amyotrophic lateral...
The tumor suppressor gene p53 has been implicated in the induction of apoptosis dividing cells. We now show that overexpression using an adenoviral vector cultured rat hippocampal pyramidal neurons causes widespread neuronal death with features typical apoptosis. did not induce p21, bax, or mdm2 neurons. X-irradiation induced immunoreactivity and cell associated Overexpression a constitutively active nonphosphorylatable form retinoblastoma product blocked x-irradiation-induced death....
Neurodegeneration associated with Alzheimer's disease is believed to involve toxicity beta-amyloid (A beta) and related peptides. Treatment of cultured rat hippocampal neurons A beta 1-40 (1 microM) or the active fragment 25-35 for 5 days led a approximately 40-50% decrease in neuronal viability. The hydrophilic antioxidant ascorbic acid (300 lipophilic 2-mercaptoethanol (10 both protected significantly against neurotoxicity. Despite protective effects these antioxidants, acute chronic...
Most early onset cases of familial Alzheimer's disease (AD) are caused by mutations in presenilin-1 (PS1) and presenilin-2 (PS2). These lead to increased beta-amyloid formation may induce apoptosis some model systems. Using primary cultured hippocampal neurons (HNs) rat pheochromocytoma (PC12) cells transiently transfected with replication-defective recombinant adenoviral vectors expressing wild-type or mutant PS1, we demonstrate that PS1s apoptosis, downregulate the survival factor Akt/PKB,...
Abstract The functional and structural characteristics of the neuromuscular junction were studied in anconeus muscle biopsies 10 patients with amyotrophic lateral sclerosis (ALS). Intracellular recordings revealed decreased amplitudes miniature endplate potentials (MEPPs). MEPP frequencies highly variable ALS but average frequency was not different from that control patients. mean quantal content ( m ), quanta available for immediate release n stores N ) all decreased. In contrast,...
Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and ∼25% FALS caused by mutations in Cu/Zn superoxide dismutase type 1 (SOD1). Mutant (MT) SOD1 is thought to be pathogenic because it misfolds aggregates. A number transgenic mice have been generated that express different MTSOD1s as transgenes exhibit an ALS-like disease. Although one study found overexpression human wild-type (WT) did not affect disease G85R mice, more recent reports claim WTSOD1 other...
Surgical management of cryptoglandular fistulas is a challenge because the consequences anal surgery potentially include fecal incontinence and impaired quality life.To assess factors associated with after for simple complex to determine impact on life.The design retrospective cross-sectional.This study was conducted at an academic tertiary center private specializing in proctologic surgery.All patients who underwent preoperative endoanal ultrasound fistula between 2002 2012.A questionnaire...
Abstract Apical dendrites of Betz cells are important sites for the integration cortical input, however their health has not been fully assessed in ALS patients. We investigated primary motor cortices isolated from post-mortem normal control subjects, patients with familial (fALS), sporadic (sALS), frontotemporal dementia (FTD-ALS), and Alzheimer’s disease (AD), found profound apical dendrite degeneration both fALS sALS, as well FTD-ALS In contrast, AD controls retain cellular integrity...
A number of neurologic diseases associated with expanded nucleotide repeats, including an inherited form amyotrophic lateral sclerosis, have unconventional translation called repeat-associated non-AUG (RAN) translation. It has been speculated that the repeat regions in RNA fold into secondary structures a length-dependent manner, promoting RAN Repeat protein products are translated, accumulate, and may contribute to disease pathogenesis. Nucleotides flank region, especially ones closest...
Abstract: Staurosporine (0.03–0.5 µ M ) induced a dose‐dependent, apoptotic degeneration in cultured rat hippocampal neurons that was sensitive to 24‐h pretreatments with the protein synthesis inhibitor cycloheximide (1 or cell cycle mimosine (100 ). To investigate role of Ca 2+ and reactive oxygen species staurosporine‐induced neuronal apoptosis, we overexpressed calbindin D 28K , binding protein, Cu/Zn superoxide dismutase, an antioxidative enzyme, using adenovirus‐mediated gene transfer....