A5101844006- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Genetic Mapping and Diversity in Plants and Animals
- Congenital Anomalies and Fetal Surgery
- Cannabis and Cannabinoid Research
- Pancreatitis Pathology and Treatment
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Genetic diversity and population structure
- Chromosomal and Genetic Variations
- Parkinson's Disease Mechanisms and Treatments
- Restless Legs Syndrome Research
- Phagocytosis and Immune Regulation
- Wheat and Barley Genetics and Pathology
- Intestinal Malrotation and Obstruction Disorders
- Congenital gastrointestinal and neural anomalies
University of Helsinki
2014-2022
All forms of diabetes mellitus (DM) are characterized by the loss functional pancreatic β cell mass, leading to insufficient insulin secretion. Thus, identification novel approaches protect and restore cells is essential for development DM therapies. Mesencephalic astrocyte-derived neurotrophic factor (MANF) an endoplasmic reticulum (ER)-stress-inducible protein, but its physiological role in mammals has remained obscure. We generated MANF-deficient mice that strikingly develop severe due...
There is a great need to identify factors that could protect pancreatic beta cells against apoptosis or stimulate their replication and thus prevent reverse the development of diabetes. One potential candidate mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum (ER) stress inducible protein. Manf knockout mice used as model diabetes develop condition because increased reduced proliferation cells, apparently related ER stress. Given this novel association...
Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss β-cell mass and insulin-dependent diabetes in mice. Similar Manf−/− mice, embryonic ablation MANF specifically from the pancreas results diabetes. In this study, we assessed importance for expansion pancreatic adult maintenance Detailed analysis Pdx-1Cre+/−::Manffl/fl mice revealed mosaic expression pancreata a significant correlation between number MANF-positive β-cells individual...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine (CDNF) form a family of atypical growth factors discovered for their neuroprotective properties in the central nervous system (CNS) animal models neurodegenerative diseases. Although mechanism protective action still remains unclear, it has been suggested that both MANF CDNF promote cell survival through regulating unfolded protein response (UPR), thereby relieving endoplasmic reticulum (ER) stress. Recent...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) resident protein with neuroprotective effects. Previous studies have shown that MANF expression altered in the developing rodent cortex a spatiotemporal manner. However, role of mammalian neurogenesis not known. The aim this study was to determine neural stem cell (NSC) proliferation, differentiation, and cerebral development. We found highly expressed lineage cells, including NSCs brain. discovered...
Cerebral dopamine neurotrophic factor (CDNF) is a that has beneficial effects on neurons in both vitro and vivo models of Parkinson's disease (PD). CDNF was recently tested phase I-II clinical trials for the treatment PD, but mechanisms underlying its neuroprotective properties are still poorly understood, although studies have suggested role regulation endoplasmic reticulum (ER) homeostasis unfolded protein response (UPR). The aim this study to investigate mechanism action through analyzing...
Cerebral dopamine neurotrophic factor (CDNF) is neuroprotective for nigrostriatal neurons and restores dopaminergic function in animal models of Parkinson's disease (PD). To understand the role CDNF mammals, we generated knockout mice (Cdnf-/-), which are viable, fertile, have a normal life-span. Surprisingly, an age-dependent loss enteric occurs selectively submucosal but not myenteric plexus. This neuronal consequence increased apoptosis neurodegeneration autophagy. Quantitatively,...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) localized protein that regulates ER homeostasis and unfolded response (UPR). The biology of endogenous MANF in the mammalian brain unknown therefore we studied phenotype MANF-deficient female male mice at different ages focusing on midbrain dopamine system cortical neurons. We show a lack from led to chronic activation UPR by upregulation endoribonuclease activity inositol-requiring enzyme 1α (IRE1α)...
Background & AimsRET, the receptor for glial cell line–derived neurotrophic factor (GDNF) family ligands, is most frequently mutated gene in congenital aganglionic megacolon or Hirschsprung's disease (HSCR). The leading cause of mortality HSCR HSCR-associated enterocolitis (HAEC), which characterized by altered mucin composition, retention, bacterial adhesion to enterocytes, and epithelial damage, although order these events obscure. In mice, loss GDNF signaling leads a severely...