A5012789643- Neuroinflammation and Neurodegeneration Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Amyotrophic Lateral Sclerosis Research
- Immune cells in cancer
- Parkinson's Disease Mechanisms and Treatments
- Immune Cell Function and Interaction
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- IL-33, ST2, and ILC Pathways
- Zebrafish Biomedical Research Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neurogenetic and Muscular Disorders Research
- Autoimmune and Inflammatory Disorders Research
- Polyomavirus and related diseases
- Lysosomal Storage Disorders Research
- Ion Transport and Channel Regulation
- Stress Responses and Cortisol
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
- Cellular transport and secretion
- interferon and immune responses
- Genetic Neurodegenerative Diseases
- Immune Response and Inflammation
- Mitochondrial Function and Pathology
University of Eastern Finland
2008-2024
Harvard University
2014-2022
Brigham and Women's Hospital
2014-2022
This work demonstrates how increased activity of copper-zinc superoxide dismutase (SOD1) paradoxically boosts production toxic reactive oxygen species (ROS) in the intermembrane space (IMS) mitochondria. Even though SOD1 is a cytosolic enzyme, fraction it found IMS, where thought to provide protection against oxidative damage. We that controls cytochrome c-catalyzed peroxidation vitro when available. The presence significantly rate ROS mitoplasts, which are devoid outer membrane and IMS. In...
Abstract Background Granulocyte colony stimulating factor (GCSF) is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, a mouse model amyotrophic lateral sclerosis (ALS). ALS fatal disease manifestations upper and lower motoneuron death muscle atrophy accompanied by inflammation the CNS periphery. Methods Human mutant G93A superoxide dismutase (SOD1) mice were treated pegfilgrastim starting at presymptomatic...
The T cell receptor (TCR) controls the cellular adaptive immune response to antigens, but our understanding of TCR repertoire diversity and challenge is still incomplete. For example, clones shared by different individuals with minimal alteration germline gene sequences (public clones) are detectable in all vertebrates, their significance unknown. Although small size, zebrafish controlled processes similar those operating mammals. Thus, we studied its stimulation self foreign antigens. We...
Protein disulfide isomerase (PDI) is an oxidoreductase assisting oxidative protein folding in the endoplasmic reticulum of all types cells, including neurons and glia. In neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), up-regulation PDI important part unfolded response (UPR) that thought to represent adaption reaction thereby protect neurons. Importantly, studies on animal models familial ALS with mutant Cu/Zn superoxide dismutase 1 (SOD1) have shown SOD1 astrocytes...
Aims: Protein misfolding occurs in neurodegenerative diseases, including Parkinson's disease (PD). In endoplasmic reticulum (ER), an overload of misfolded proteins, particularly alpha-synuclein (αSyn) PD, may cause stress and activate the unfolded protein response (UPR). This UPR includes activation chaperones, such as disulphide isomerase (PDI), which assists refolding contributes to removal proteins. Although up-regulation PDI is considered a protective response, its coupled with increased...
Stroke is a leading cause of permanent disability worldwide. Despite intensive research over the last decades, key anti-inflammatory strategies that have proven beneficial in pre-clinical animal models often failed translation. The importance neutrophils as pro- and peripheral immune cells has been overlooked ischemic stroke. However, rapidly infiltrate into brain parenchyma after stroke secrete an array pro-inflammatory factors including reactive oxygen species, proteases, cytokines,...
Ischemic stroke is one of the main causes death and disability worldwide. It caused by cessation cerebral blood flow resulting in insufficient delivery glucose oxygen to neural tissue. The inflammatory response initiated ischemic order restore tissue homeostasis acute phase contributes delayed brain damage.By using vitro models neuroinflammation vivo model permanent middle artery occlusion, we demonstrate neuroprotective anti-inflammatory effects sulfosuccinimidyl oleate sodium (SSO).SSO...
Abstract The Finnish-variant late infantile neuronal ceroid lipofuscinosis, also known as CLN5 disease, is caused by mutations in the gene. Cln5 strongly expressed developing brain and expression continues into adulthood. CLN5, a protein of unknown function, implicated neurodevelopment but detailed investigation lacking. Using Cln5−/− embryos various ages cells harvested from brains we investigated hitherto role brain. Loss results differentiation deficits delays interneuron development...
This protocol details the induction of inflammation and acute myelin degeneration in larval zebrafish with a duration <10 days. We describe use this model to screen effects candidate compounds on inflammation, followed by RNA isolation, qPCR-based quantification gene expression. then outline steps for bioinformatic analysis mechanisms associated compounds. can be used combination drugs genetic targeting identify pathways that contribute neurodegeneration. For complete execution profile,...