A5091418471- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Adenosine and Purinergic Signaling
- Phagocytosis and Immune Regulation
- RNA modifications and cancer
- Transgenic Plants and Applications
- Autism Spectrum Disorder Research
- Galectins and Cancer Biology
- Pancreatic function and diabetes
- Neurological disorders and treatments
- Genetics and Neurodevelopmental Disorders
- Pancreatitis Pathology and Treatment
- RNA Research and Splicing
University of Helsinki
2015-2023
Czech Academy of Sciences, Institute of Biotechnology
2020
Biocenter Finland
2015
Tallinn University of Technology
2011
Background Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2) is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG). While involved in the development and functioning of many different cell types, recent studies point important roles for TCF4 nervous system. Specifically, human gene implicated susceptibility schizophrenia haploinsufficiency cause Pitt-Hopkins mental retardation syndrome. However, structure, expression coding potential have...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in neurons and pancreatic β cells vitro models of neurodegeneration diabetes vivo. However, the exact mode MANF action has remained elusive. Here, we show that directly interacts ER transmembrane unfolded response (UPR) sensor IRE1α, identify binding interface between IRE1α. The expression wild-type MANF, but not its IRE1α binding-deficient mutant,...
Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved factors. We demonstrate for the first time therapeutic effect CDNF in unilateral 6-hydroxydopamine (6-OHDA) lesion model Parkinson's disease marmoset monkeys. Furthermore, we tested impact high chronic doses human recombinant on unlesioned monkeys and analyzed amino acid sequence CDNF. The severity 6-OHDA lesions treatment effects were monitored vivo using 123I-FP-CIT (DaTSCAN)...
Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) an ER-localized protein whose expression secretion induced by ER a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due lack knowledge receptor. Here we show that Neuroplastin (NPTN) such receptor for MANF. Biochemical analysis shows physiological...
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-regulated protein exhibiting cytoprotective properties through a poorly understood mechanism in various vitro and vivo models of neuronal non-neuronal damage. Although initially characterized as secreted for midbrain dopamine neurons, MANF has recently gained more interest its intracellular role regulating the ER homeostasis, including serving cofactor chaperone glucose-regulated 78 (GRP78). We...
Abstract Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a prosurvival protein that protects the cells when applied intracellularly in vitro or extracellularly vivo . Its protective mechanisms are poorly known. Here we studied role of two short sequence motifs within carboxy-(C) terminal domain MANF its neuroprotective activity: CKGC (a CXXC motif) could be involved redox reactions, and C-terminal RTDL sequence, an endoplasmic reticulum (ER) retention signal. We mutated these...
A molecular hallmark in Parkinson's disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth that mostly resident the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of beneficial CDNF can be protecting neurons from toxic α-synuclein. Here, we investigated on aggregation vitro vivo. We found directly interacts with a KD = 23 ± 6 nM reduces auto-association. Using nuclear magnetic...
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...
Abstract Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located protein with cytoprotective effects in numerous cell types vitro and models of neurodegeneration diabetes vivo . So far, the exact mode its action has remained elusive plasma membrane or ER-located receptors MANF have not been identified. We found that can directly interact transmembrane unfolded response (UPR) receptor IRE1α compete major ER chaperone BiP (GRP78) for interaction...
Endoplasmic reticulum (ER) stress plays a crucial role in the pathogenesis of various common diseases, such as diabetes mellitus and neurodegenerative disorders, well rare inherited diseases including Wolfram syndrome. ER is known to induce pro-inflammatory response ultimately leads apoptotic cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) an ER-localized protein whose expression secretion induced by stress, which turn alleviates inflammation. Although multiple studies...