- Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). (biomedcentral.com)
- Cytoplasmic FUS inclusions have also been identified in a subset of frontotemporal lobar degeneration (FTLD-FUS). (cipsm.de)
- For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
- The role of HSP27 in the pathogenesis of neurodegenerative disorders such as frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD) and motor neuron disease (MND) was investigated. (biomedcentral.com)
- and tau, TDP-43 and fused in sarcoma in frontotemporal lobar degeneration (FTLD). (biomedcentral.com)
- The microtubule-associated protein tau gene (MAPT) 10+16 intronic mutation causes frontotemporal lobar degeneration (FTLD) by increasing expression of four-repeat (4R)-tau isoforms. (crick.ac.uk)
- OBJECTIVE: There is increasing evidence that common genetic risk factors underlie frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). (unito.it)
- Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). (peixotolab.org)
- article{Benussi2021, abstract = {Dysfunctions in the endo-lysosomal system have been hypothesized to underlie neurodegeneration in major neurocognitive disorders due to Alzheimer's disease (AD), Frontotemporal Lobar Degeneration (FTLD), and Lewy body disease (DLB). (dissem.in)
- The condition described in the North American literature as primary progressive aphasia and that described in the European literature as frontal dementia have been combined under the term frontotemporal lobe dementia (FTD) or frontotemporal lobar degeneration (FTLD). (medscape.com)
- An expanded GGGGCC repeat in a non-coding region of the C9orf72 gene is a common cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis. (nih.gov)
- Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a pre-senile onset. (touchneurology.com)
- Frontotemporal lobar degeneration (FTLD) occurs most often in the pre-senile period, and age at onset is typically 45-65 years, with a mean in the 50s. (touchneurology.com)
- The current consensus criteria 3 identify three clinical syndromes: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD), which reflect the clinical heterogeneity of FTLD. (touchneurology.com)
- Reducing-edge analysis suggests endosomal/immune dysregulation in GRN / C9orf72 -associated frontotemporal lobar degeneration (FTLD). (teitell-lab.com)
- Transactive response DNA-binding protein 43 (TDP-43)-induced neurotoxicity is currently well recognized as a contributor to the pathology of amyotrophic lateral sclerosis (ALS), and the deposition of TDP-43 has been linked to other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). (dgist.ac.kr)
- Berberine has been implicated in several kinds of diseases, including the neuronal-related pathogenesis, such as Parkinson's, Huntington's and Alzheimer's diseases. (biomedcentral.com)
- Degeneration of human orexinergic neurons across Braak stages of Alzheimer's disease: Implication for pathogenesis, sleep dysfunction, and therapy. (ucsf.edu)
- In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. (biomedcentral.com)
- Despite the majority of AD and FTLD cases being sporadic and likely caused by the interaction between genetic and environmental factors, so far it has been observed that clinically typical AD and FTLD can cluster in families and be inherited in an autosomal dominant fashion, suggesting a genetic cause. (touchneurology.com)
- Hence, it is possible that wtSOD1 may be a contributor to disease pathogenesis in sporadic ALS. (nature.com)
- On this retrospective examine, we investigated plasma small extracellular vesicles (sEVs) and complement proteins in 172 topics (40 Sporadic FTLD, 40 Intermediate/Pathological C9orf72 enlargement carriers, and 49 Heterozygous/Homozygous GRN mutation carriers, 43 controls). (teitell-lab.com)
- We demonstrated that genetic/sporadic FTLD share decrease sEV concentrations and better sEV sizes. (teitell-lab.com)
- A genetic aetiology has been identified in up to 20% of apparently "sporadic" and 60% of familial ALS cases, in which two or more family members are clinically affected, with at least 16 genes and genetic loci implicated in ALS pathogenesis. (acnr.co.uk)
- Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS. (biomedcentral.com)
- Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. (cipsm.de)
- In addition to FUS, the two other members in the FET protein family members, Ewing's sarcoma (EWS) and TATA-binding protein-associated aspect 15 (TAF15), have also been discovered to label a proportion of pathological inclusions in FTLD-FUS [40]. (itkinhibitor.com)
- Nevertheless, it really is not simply FET proteins which have been identified as components of pathological inclusions in FTLD-FUS instances. (itkinhibitor.com)
- Our group previously reported several other RNA binding proteins are present to varying degrees within these inclusions following pathological and biochemical evaluation with the heterogeneous nuclear ribonucleoprotein (hnRNP) family members of proteins in FTLD-FUS cases [17]. (itkinhibitor.com)
- Given that hnRNPs perform a diverse array of functions linked to RNA metabolism, the presence of several hnRNPs in FUS inclusions implies that the pathogenesis of FTLD-FUS extends beyond FET proteins, TRN1 cargoes and dysfunctional nuclear import, and implicates a wider dysregulation of RNA binding pr. (itkinhibitor.com)
- Although these studies have provided insights into individual components of the neuro-motor network at specific time points in disease pathogenesis, there remains a need to define the onset and progression of neuronal pathology at successive stages of disease in ALS in key subcortical structures receiving cortical outputs: the striatum, hippocampus ( Spalloni and Longone, 2015 ), brainstem, and spinal cord. (frontiersin.org)
- The purpose of our study was to evaluate the frequency of SQSTM1 mutations in a dataset of unrelated patients with FTLD or ALS, in comparison with healthy controls and patients with Paget disease of bone (PDB). (unito.it)
- The clinical characteristics of patients with FTLD or ALS with gene mutations were examined. (unito.it)
- RESULTS: We identified 6 missense mutations in the coding region of SQSTM1 in patients with either FTLD or ALS, none of which were found in healthy controls or patients with PDB. (unito.it)
- CONCLUSIONS: SQSTM1 mutations are present in patients with FTLD and patients with ALS. (unito.it)
- 2019. ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway. . (cornell.edu)
- We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies. (cipsm.de)
- Genes responsible for familial AD include the amyloid precursor protein ( APP ), presenilin 1 ( PS1 ) and presenilin 2 ( PS2 ), whereas the main genes responsible for familial FTLD are microtubule-associated protein tau gene ( MAPT ) and progranulin ( GRN ). (touchneurology.com)
- Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. (benthamscience.com)
- In AD, DLB, and FTLD patients and in controls (948 subjects), we performed a targeted sequencing of the top 50 genes belonging to the endo-lysosomal pathway. (dissem.in)
- Our data highlight that genes controlling key endo-lysosomal processes (i.e., protein sorting/transport, clathrin-coated vesicle uncoating, lysosomal enzymatic activity regulation) might be involved in AD, FTLD and DLB pathogenesis, thus suggesting an etiological link behind these diseases. (dissem.in)
- METHODS: Promoter region and all exons of SQSTM1 were sequenced in a large group of subjects, including patients with FTLD or ALS, healthy controls, and patients with PDB. (unito.it)
- Furthermore, 7 novel noncoding SQSTM1 variants were found in patients with FTLD and patients with ALS, including 4 variations in the promoter region. (unito.it)
- In FTLD the deposition of tau has been observed in a number of cases, but in several brains there is no deposition of tau but instead a positivity for ubiquitin. (touchneurology.com)
- This observation has led for the hypothesis that disruption of the nuclear import of FET proteins by TRN1 could be contributing to pathogenesis in FTLD-FUS [43]. (itkinhibitor.com)
- 2017. Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus-dystonia syndrome . (cardiff.ac.uk)
- A number of additional genetic factors contribute to susceptibility for AD and FTLD. (touchneurology.com)
- His studies in the multiple aspects of developmental biology and early nervous system development are key to gaining a greater insight into the pathogenesis of human diseases, including brain malformations, mental retardation, epilepsy and autism. (blogspot.com)
- These data establish that sense and antisense C9orf72 repeat RNA foci are a consistent and specific feature of C9FTLD, providing new insight into the pathogenesis of C9FTLD. (nih.gov)
- Accumulation of TDP-43 within the Ub-positive insoluble aggregates implies that mis-regulation of the metabolism of TDP-43, including Ub-proteasome and autophagy pathways, plays a causative role in the pathogenesis. (biomedcentral.com)
- Spatiotemporal proteomic analysis of stress granule disassembly using APEX reveals regulation by SUMOylation and links to ALS pathogenesis[J]. Mol Cell, 2020, 80: 876-891 e6. (magtechjournal.com)
- En los últimos años he compaginado mi labor investigadora con la actividad docente, y con labores de gestión: Subdirectora del Departamento de Farmacología, Universidad de Navarra (2009-12), Directora del Departamento de Farmacología y Toxicología, Universidad de Navarra (2012-2014) y Vicedecana (2014-2020) y Decana (2020- actualidad) de la Facultad de Farmacia y Nutrición, Universidad de Navarra. (unav.edu)
- La estancia postdoctoral que disfruté en el Dementia Research Laboratory (King's College, Londres), me permitió, además de desarrollar mi habilidades técnicas e intelectuales, el ponerme en contacto y comenzar colaboraciones de investigación, que se mantiene a dia de hoy. (unav.edu)
- Thus, identification of the potential drugs targeting on modulating the TDP-43 metabolism pathway might be a potential therapeutic strategy for FTLD-U and ALS patients with TDP-43 proteinopathies. (biomedcentral.com)
- Patients with AD and FTLD were affected more often, and showed greater immunostaining for HSP27, than patients with MND and controls. (biomedcentral.com)
- Introduction to Veri-T: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Verdiperstat in Patients with svPPA Due to FTLD-TDP. (ucsf.edu)
- These results gave us the notion that inhibition of autophagy by 3-MA reverses the effect of berberine on TDP-43 pathogenesis, and activation of mTOR-regulated autophagy plays an important role in berberine-mediated therapeutic effect on TDP-43 proteinopathies. (biomedcentral.com)
- To comprehend Ubqln2 pathogenesis we should examine most important query whether pathogenically mutated Ubqln2 causes neuron loss of life mainly with a gain or lack of features. (bioinf.org)
- We investigated the potential role for astrocytes in the pathogenesis of FTLD by studying the expression of 4R-tau. (crick.ac.uk)
- Additional studies are warranted in order to better investigate the role of p62 in the pathogenesis of both FTLD and ALS. (unito.it)
- The pattern of HSP27 immunostaining observed may reflect the extent of ongoing neurodegeneration in affected brain areas and is not specific to FTLD, AD or MND. (biomedcentral.com)
- Western blot analysis revealed higher HSP27 expression in FTLD than in controls, but without qualitative differences in banding patterns. (biomedcentral.com)
- The pathogenesis of HS remains unknown, with both ischemic and neurodegenerative theories proposed. (gp120inhibitor.com)
- Background: Cytokines are known to play critical roles in the pathogenesis of chronic hepatitis B (CHB). (jakenzyme.com)