A5031788033- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Syndromes and Imprinting
- Genetics and Neurodevelopmental Disorders
- Neurological Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Immune cells in cancer
- Genetic Neurodegenerative Diseases
- Regulation of Appetite and Obesity
- Parkinson's Disease Mechanisms and Treatments
- Adipokines, Inflammation, and Metabolic Diseases
- Ubiquitin and proteasome pathways
- Genetic and Kidney Cyst Diseases
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Neurological and metabolic disorders
- Tryptophan and brain disorders
- Autism Spectrum Disorder Research
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Prenatal Screening and Diagnostics
- Adipose Tissue and Metabolism
- Hedgehog Signaling Pathway Studies
- Neurological disorders and treatments
Van Andel Institute
2023-2025
National Brain Research Centre
2014-2019
There are no approved treatments that slow Parkinson's disease (PD) progression and therefore it is important to identify novel pathogenic mechanisms can be targeted. Loss of the epigenetic marker, Tet2 appears have some beneficial effects in PD models, but underlying mechanism action not well understood. We performed an unbiased transcriptomic analysis cortical neurons isolated from patients with dysregulated pathways determine their potential contributions process. discovered genes...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in memory and cognitive function. Pathological hallmark of AD includes aberrant aggregation amyloid beta (Aβ) peptide, which produced upon sequential cleavage precursor protein (APP) β- γ -secretases. On the contrary, α-secretase cleaves APP within Aβ sequence thereby prevents generation. Here, we investigated role ubiquitin ligase Ube3a (involved synaptic function plasticity) pathogenesis using...
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal expansion of CAG repeats in the gene encoding huntingtin. Mutant huntingtin undergoes proteolytic processing and its N-terminal fragment containing polyglutamine repeat accumulates as inclusion not only nucleus but also cytoplasm neuronal processes. Here, we demonstrate that removal ubiquitin ligase Ube3a selectively from HD mice brain resulted accelerated phenotype shorter lifespan comparison with mice....
The expression of ubiquitin ligase UBE3A is paternally imprinted in neurons and loss function maternally inherited causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe intellectual disability motor disturbances. Over activation also linked with autism. Mice deficient for maternal Ube3a (AS mice) exhibit various behavioral features AS including cognitive deficits although the underlying molecular mechanism poorly understood. Here, we investigated possible...
Angelman syndrome (AS) is a neurodevelopmental disorder categorized by severe disability in intellectual functions and affected the loss of function maternally inherited UBE3A gene. Mice deficient for maternal Ube3a recapitulates many distinguishing behavioral features AS used as typical model system to understand disease pathogenic mechanism. Here, we first show significant increase HDAC1 HDAC2 activities mice brain from early embryonic day 16(E16). In depth study further reveals that...
Chronic high-fat feeding triggers chronic metabolic dysfunction including obesity, insulin resistance, and diabetes. How intake first these pathophysiological states remains unknown. Here, we identify an acute microglial response that rapidly translates of diet (HFD) to a surprisingly beneficial effect on metabolism spatial / learning memory. High-fat increases palmitate levels in cerebrospinal fluid wave activation characterized by mitochondrial membrane fission as well skewing towards...
Chronic high-fat feeding triggers metabolic dysfunction including obesity, insulin resistance, and diabetes. How intake first these pathophysiological states remains unknown. Here, we identify an acute microglial response that rapidly translates of diet (HFD) to a surprisingly beneficial effect on metabolism spatial/learning memory. High-fat increases palmitate levels in cerebrospinal fluid wave activation characterized by mitochondrial membrane fission as well skewing toward aerobic...
Huntington's disease (HD) is a dominantly inherited progressive neurodegenerative disorder caused by the accumulation of polyglutamine expanded mutant huntingtin as inclusion bodies primarily in brain. After discovery HD gene, considerable progress has been made understanding pathogenesis and multiple drug targets have identified, even though currently there no effective therapy. Here, we demonstrate that treatment topotecan, brain-penetrating topoisomerase 1 inhibitor, to transgenic mouse...
Chronic high-fat feeding triggers widespread metabolic dysfunction including obesity, insulin resistance, and diabetes. While these ultimate pathological states are relatively well understood, we have a limited understanding of how intake first physiological changes. Here, identify an acute microglial response that rapidly translates diet (HFD) to surprisingly beneficial effect on spatial learning memory. Acute increases palmitate levels in cerebrospinal fluid wave activation characterized...
Chronic high-fat feeding triggers chronic metabolic dysfunction including obesity, insulin resistance, and diabetes. How intake first these pathophysiological states remains unknown. Here, we identify an acute microglial response that rapidly translates of diet (HFD) to a surprisingly beneficial effect on metabolism spatial / learning memory. High-fat increases palmitate levels in cerebrospinal fluid wave activation characterized by mitochondrial membrane fission as well skewing towards...
ABSTRACT There are no approved treatments that slow Parkinson’s disease (PD) progression and therefore it is important to identify novel pathogenic mechanisms can be targeted. Loss of the epigenetic marker, Tet2 appears have some beneficial effects in PD models, but underlying mechanism action not well understood. We performed an unbiased transcriptomic analysis cortical neurons isolated from patients with dysregulated pathways determine their potential contributions process. discovered...
This is a protocol for immunocytochemistry 24 and 96 well cell culture plates.
Chronic high-fat feeding triggers metabolic dysfunction including obesity, insulin resistance, and diabetes. How intake first these pathophysiological states remains unknown. Here, we identify an acute microglial response that rapidly translates of diet (HFD) to a surprisingly beneficial effect on metabolism spatial/learning memory. High-fat increases palmitate levels in cerebrospinal fluid wave activation characterized by mitochondrial membrane fission as well skewing toward aerobic...
Abstract Background Pathologic heterogeneity is a hallmark of Lewy body dementia (LBD), yet the impact pathology on co-pathologies poorly understood. pathology, containing α-synuclein, often associated with regional tau burden in LBD. Similarly, granulovacuolar degeneration bodies (GVBs) have been Alzheimer’s disease. Interestingly, GVBs detected broad range neurodegenerative conditions including both α-synucleinopathies and tauopathies. Despite frequent co-occurrence, little known about...
ABSTRACT α-Synuclein misfolding and progressive accumulation drives a pathogenic process in Parkinson’s disease. To understand cellular network vulnerability to α-synuclein pathology, we developed framework quantify network-level identify new therapeutic targets at the level. Full brain pathology was mapped mice over 9 months. Empirical data compared theoretical estimates from diffusion model of progression along anatomical connections. Unexplained variance enabled us derive regional that...