A5069937879- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Neurogenesis and neuroplasticity mechanisms
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- Adenosine and Purinergic Signaling
- Phagocytosis and Immune Regulation
- Neurological diseases and metabolism
- Inflammation biomarkers and pathways
- Tryptophan and brain disorders
- Neurological Disease Mechanisms and Treatments
- Barrier Structure and Function Studies
- Neonatal and fetal brain pathology
- Parkinson's Disease Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Calcium signaling and nucleotide metabolism
- Regulation of Appetite and Obesity
Achucarro Basque Center for Neuroscience
2016-2024
University of the Basque Country
2016-2024
Ludwig-Maximilians-Universität München
2023-2024
Roche (Switzerland)
2021-2024
Euskadiko Parke Teknologikoa
2016
During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, found neurogenesis was disrupted male female mice chronically deficient for two pathways: purinergic receptor P2Y12, tyrosine kinases TAM family Mer kinase (MerTK)/Axl. In contrast,...
Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role the diseased brain poorly explored. Recent findings suggest that adult hippocampal neurogenic niche, where excess newborn cells undergo apoptosis physiological conditions, phagocytosis efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes as well, we confronted them with series apoptotic challenges discovered...
Microglia are key in the homeostatic well-being of brain and microglial dysfunction has been implicated neurodegenerative disorders such as Alzheimer's disease (AD). Due to many limitations study microglia situ or isolated for large scale drug discovery applications, there is a high need develop robust scalable human cellular models with reliable translatability disease. Here we describe generation microglia-like cells from induced pluripotent stem (iPSC) distinct phenotypes mechanistic...
Abstract Microglia, the immune cells of central nervous system, continuously survey brain to detect alterations and maintain tissue homeostasis. The motility microglial processes is indicative their surveying capacity in normal pathological conditions. gold standard technique study involves use two‐photon microscopy obtain time‐lapse images from slices or cortex living animals. This generates four dimensionally‐coded which are analyzed manually using time‐consuming, non‐standardized...
Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43) pathology (FTLD- GRN ). Multiple therapeutic strategies are in clinical development to restore PGRN the CNS, including gene therapy. However, limitation of current therapy approaches aimed alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution. We therefore developed an adeno-associated virus (AAV) targeting...
Abstract Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology (FTLD- GRN ). Multiple therapeutic strategies are in clinical development to restore PGRN levels the CNS, including gene therapy. However, limitation of current therapy approaches aimed alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution. We therefore developed an adeno-associated virus (AAV) targeting liver (L)...
SUMMARY During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent spillover their intracellular contents. Here, we propose that phagocytosis is not merely a passive process corpse removal but has an active role in maintaining neurogenesis. First, found neurogenesis was disrupted mice chronically deficient for two microglial pathways (P2Y12 MerTK/Axl), transiently increased which MerTK expression...
ABSTRACT Phagocytosis is an indispensable function of microglia, the brain professional phagocytes. Microglia are particularly efficient phagocytosing cells that undergo programmed cell death (apoptosis) in physiological conditions. However, mounting evidence suggests microglial phagocytosis dysfunction multiple disorders. These observations prompted us to search for modulators (enhancers or inhibitors) with therapeutic potential. We used a bottom-up strategy consisted on identification...
Phagocytosis is an indispensable function of microglia, the brain professional phagocytes. Microglia particularly efficient phagocytosing cells that undergo programmed cell death (apoptosis) in physiological conditions. However, mounting evidence suggests microglial phagocytosis dysfunction multiple disorders. These observations prompted us to search for modulators (enhancers or inhibitors) with therapeutic potential. We used a bottom-up strategy consisted on identification using phenotypic...