A5011963571- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Genetics and Neurodevelopmental Disorders
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- RNA regulation and disease
- Phagocytosis and Immune Regulation
- Parkinson's Disease Mechanisms and Treatments
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Vestibular and auditory disorders
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience of respiration and sleep
- Erythrocyte Function and Pathophysiology
- Muscle Physiology and Disorders
- Immune Response and Inflammation
- Cell death mechanisms and regulation
- Mental Health Treatment and Access
- Neurological disorders and treatments
- RNA modifications and cancer
- Autoimmune Neurological Disorders and Treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Nasolacrimal Duct Obstruction Treatments
University of Minnesota
2016-2025
Massachusetts General Hospital
2023
University of Minnesota System
2022
Klinički centar Niš
2020
Northwestern University
2007-2012
University of Illinois Urbana-Champaign
2002-2006
University of Illinois Chicago
2002-2006
Illinois College
2002-2006
Abstract Physiological cell death is a process the purpose of which elimination functionally inappropriate cells in manner that does not elicit an inflammatory response. We have shown previously ability apoptotic corpses to be recognized by macrophages and modulate proinflammatory responses those represents paradoxically gain-of-function acquired during physiological process. Cells die pathologically (that is, necrotic vs corpses) also are but do down-regulate macrophage responses;...
Polyglutamine (polyQ) expansion in the protein Ataxin-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), a fatal dominantly inherited neurodegenerative disease characterized by motor deficits, cerebellar neurodegeneration, and gliosis. Currently, there are no treatments available to delay or ameliorate SCA1. We have examined effect of depleting microglia during early stage using PLX, an inhibitor colony-stimulating factor receptor (CSFR1), on severity mouse model Transgenic SCA1,...
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an abnormal expansion of CAG repeats in the Ataxin-1 (ATXN1) gene and characterized motor deficits cerebellar neurodegeneration. Even though mutant ATXN1 expressed from early age, onset usually occurs patient's mid-thirties, indicating presence compensatory factors that limit toxic effects disease. Brain derived neurotrophic factor (BDNF) growth known to be important for survival function neurons. Using...
Heterogeneity is one of the key features healthy brain and selective vulnerability characterizes many, if not all, neurodegenerative diseases. While cerebellum contains majority cells, neither its heterogeneity nor in disease are well understood. Here we describe molecular, cellular functional context as cerebellar Spinocerebellar Ataxia Type 1 (SCA1). We first compared pathology vermis hemispheres across anterior to posterior axis a knock-in SCA1 mouse model. Using immunohistochemistry,...
Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced phenotypes, we developed floxed conditional knockin mouse (f-ATXN1146Q/2Q) with Atxn1 coding exons replaced human ATXN1 encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor cognitive deficits, wasting,...
Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant inherited neurodegenerative disease caused by the expansion of glutamine (Q)-encoding CAG repeats in gene ATAXIN1 (ATXN1). Patients with SCA1 suffer from movement and cognitive deficits severe cerebellar pathology. Previous studies identified sex differences progression patients, but whether these are present mouse models unclear. Using battery behavioral tests, immunohistochemistry brain slices, RNA sequencing, we examined...
The purpose of physiological cell death is the noninflammatory clearance cells that have become inappropriate or nonfunctional. Consistent with this function, recognition apoptotic by professional phagocytes, including macrophages and dendritic cells, triggers a set potent anti-inflammatory responses manifest on multiple levels. immediate-early inhibition proinflammatory cytokine gene transcription in phagocyte proximate consequence corpse, independent subsequent engulfment soluble factor...
Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in Ataxin-1 (ATXN1) gene. SCA1 characterized balance and coordination deficits due to predominant loss Purkinje neurons cerebellum. We previously demonstrated that cerebellar astrogliosis beings during early stages SCA1, prior onset motor neurons. communicate here contributes pathogenesis biphasic, stage dependent manner. modulated selectively reducing...
Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the HTT gene for which no therapies are available. mutation causes protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of basal ganglia. Transcriptional perturbations synaptic genes neuroinflammation key processes that precede MSN dysfunction motor symptom onset. Understanding interplay between these crucial to develop effective therapeutic...
Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused by a pathogenic glutamine repeat expansion in the protein ataxin-1 (ATXN1). One likely mechanism mediating pathogenesis excessive transcriptional repression induced expanded ATXN-1. Because ATXN1 binds HDAC3, Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced repression, tested whether genetically depleting HDAC3 improves phenotype of SCA1 knock-in mouse (SCA1154Q/2Q),...
Abstract Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by abnormal expansion of glutamine (Q) encoding CAG repeats in the gene Ataxin-1 (ATXN1). Although motor and balance deficits are core symptoms SCA1, cognitive decline also commonly observed patients. While mutant ATXN1 expressed throughout brain, pathological findings reveal severe atrophy cerebellar cortex SCA1 The cerebellum has recently been implicated diverse functions, yet to what extent...
Neuronal differentiation is a tightly regulated process characterized by temporal and spatial alterations in gene expression. A number of studies indicate significant role for histone acetylation the regulation genes involved development. Histone deacetylases acetyltransferases. Recent findings suggest that these catalytic activities, turn, are modulated yet another set regulators. Of considerable interest this context possible INHAT (inhibitor acetyltransferase) complex, comprised group...
Endoplasmic reticulum-associated degradation (ERAD) is a principal quality-control mechanism responsible for targeting misfolded ER proteins cytosolic degradation. Evidence suggests that impairment of ERAD contributes to neuron dysfunction and death in neurodegenerative diseases, many which are characterized by accumulation aggregation proteins. However, the physiological role neurons remains unclear. The Sel1L-Hrd1 complex consisting E3 ubiquitin ligase Hrd1 its adaptor protein Sel1L...