A5021224486- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Nicotinic Acetylcholine Receptors Study
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- 14-3-3 protein interactions
- Neurogenesis and neuroplasticity mechanisms
- Memory and Neural Mechanisms
- Long-Term Effects of COVID-19
- S100 Proteins and Annexins
- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- COVID-19 Impact on Reproduction
- Medicinal Plants and Neuroprotection
- Neuroscience and Neuropharmacology Research
- Pancreatic function and diabetes
- Infectious Encephalopathies and Encephalitis
- Biochemical Acid Research Studies
- Genomics and Rare Diseases
- Cellular transport and secretion
- Prion Diseases and Protein Misfolding
Instituto de Neurociencias
2016-2025
Biomedical Research Networking Center on Neurodegenerative Diseases
2013-2025
Hospital General Universitario de Elche
2013-2025
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
2013-2025
Consejo Superior de Investigaciones Científicas
2006-2022
Universitat de Miguel Hernández d'Elx
2008-2015
Centro de Investigacion Principe Felipe
2006
Universidad de Murcia
1999-2003
A common feature in the Alzheimer's disease (AD) brain is presence of acetylcholinesterase (AChE) which commonly associated with β-amyloid plaques and neurofibrillary tangles (NFT). Although our understanding relationship between AChE pathological features AD incomplete, increasing evidence suggests that both protein (Aβ) abnormally hyperphosphorylated tau (P-tau) can influence expression. We also review recent findings suggest possible role development a vicious cycle Aβ P-tau dysregulation...
Reelin is a glycoprotein that essential for the correct cytoarchitectonic organization of developing CNS. Its function in adult brain less understood, although it has been proposed involved signaling pathways linked to neurodegeneration. Here we analyzed expression brains and cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients nondemented controls. We found 40% increase protein levels cortex AD compared with Similar increases were detected at mRNA transcriptional level. This...
Studies of the pathogenesis hepatic encephalopathy are hampered by lack a satisfactory animal model. We examined neurological features rats after bile duct ligation fed hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, (BDL), BDL pair fed, and BDL+HD. The BDL+HD made via an ammonia-containing that began 2 weeks operation. One week later, animals sacrificed. displayed increased level cerebral ammonia neuroanatomical characteristics (HE), including...
Background Many studies have been conducted in an extensive effort to identify alterations blood cholinesterase levels as a consequence of disease, including the analysis acetylcholinesterase (AChE) plasma. Conventional assays using selective inhibitors not particularly successful excess amounts butyrylcholinesterase (BuChE) pose major problem. Principal Findings Here we estimated AChE activity human plasma by first immunoprecipitating BuChE and measuring immunodepleted Human were ∼20...
The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations the brain levels of key enzymes cirrhotic patients animal models with liver failure. An increase (∼30%) activity acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) observed cortex from deceased hepatic coma, while acetylcholine-synthesizing choline acetyltransferase, remains unaffected. In agreement human data, AChE cortical extracts bile duct...
The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications minor or non-neurological symptoms are needed understand their potential as indicators CNS injury vulnerability. Plasma fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays 45 samples from infection [moderate (n = 35),...
The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in non-amyloidogenic processing of amyloid precursor protein. This study assesses whether ADAM10 present cerebrospinal fluid (CSF), and it has potential as a biomarker for Alzheimer's disease (AD).ADAM10 was characterized human CSF samples by immunoprecipitation western blotting using antibodies specific different domains protein ultracentrifugation sucrose density gradients. Samples from AD patients (n = 20)...
This study assesses the cerebrospinal fluid (CSF) levels of viral receptor angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 fragments in patients with SARS-CoV-2 infection presenting encephalitis (CoV-Enceph). The included biobanked CSF from 18 CoV-Enceph, 4 subjects COVID-19 without (CoV), 21 non-COVID-related (Enceph), neurologically healthy controls. Participants underwent a standardized assessment for encephalitis. A large subset samples an extended panel neuronal,...
Alzheimer's disease (AD) is characterized by a decrease in the enzymatic activity of enzyme acetylcholinesterase (AChE). AChE expressed as multiple splice variants, which may serve both cholinergic degradative functions and non-cholinergic unrelated with their capacity to hydrolyze acetylcholine. We have recently demonstrated that prominent pool enzymatically inactive protein exists AD brain. In this study, we analyzed transcript levels individual variants human frontal cortex from patients...
Abstract This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer’s disease (AD). Immunoprecipitation simultaneous assay by Western blotting using multiplex fluorescence imaging with specific antibodies against particular domains served to characterize CTFs APP human CSF. We demonstrate that APP-CTFs detectable CSF, being most abundant a 25-kDa fragment, probably...
In Alzheimer's disease (AD), the enzyme acetylcholinesterase (AChE) co-localizes with hyperphosphorylated tau (P-tau) within neurofibrillary tangles. Having demonstrated that AChE expression is increased in transgenic mouse model of Tg-VLW, here we examined whether modulating phosphorylated levels by over-expressing wild-type human and glycogen synthase kinase-3β (GSK3β) influences expression. SH-SY5Y neuroblastoma cells expressing higher P-tau, activity protein (20% ± 2%) (440% 150%),...
The reelin signaling protein and its downstream components have been associated with synaptic plasticity neurotransmission. pathway begins the binding of to transmembrane lipoprotein receptor apolipopro-tein E 2 (ApoER2), which in turns induces sequential cleavage ApoER2 by action α- γ-secretases. Using conditional-knockout mice catalytic component γ-secretase complex, presenilin 1 (PS1), we demonstrated increased brain transcript levels, no changes number reelin-positive cells. human...
Background & Aims There have been many studies on plasma butyrylcholinesterase in liver dysfunction. However, no data is available about acetylcholinesterase human cirrhosis, although profound changes described cirrhotic rat models. Methods Human serum and its molecular forms were determined enzymatically, after immunodepletion. The distinct species of acetylcholinesterase, with a C-terminus, by western blotting, the level transcripts real-time PCR. Liver was also evaluated...
The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of γ-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate consequences AChE-PS1 interactions, particularly influence
Classical studies of cholinesterase activity during liver dysfunction have focused on butyrylcholinesterase (BuChE), whereas acetylcholinesterase (AChE) has not received much attention. In the current study, and plasma AChE levels were investigated in rats with cirrhosis induced after 3 weeks bile duct ligation (BDL). BDL showed a pronounced decrease (˜50%) compared sham-operated (non-ligated, NL) controls; BuChE appeared unaffected. A selective loss tetrameric (G4) was detected rats, an...
Abstract Background Presenilin-1 (PS1) is the active component of amyloid precursor protein cleaving γ-secretase complex. PS1 a transmembrane containing multiple hydrophobic regions which presence in cerebrospinal fluid (CSF) has not been measured to date. This study assesses whether and other components complex are present CSF. Results Here, we show that ventricular post-mortem lumbar ante-mortem CSF, plasma as 100–150-kDa hetero-complexes both N- C-terminal fragments (NTF CTF) protein....
Studies are needed to identify useful biomarkers assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine levels various plasma species SARS-CoV-2 host receptor, angiotensin-converting enzyme 2 (ACE2), in patients at different phases infection. Human ACE2 were characterized immunoprecipitation western blotting employing antibodies against ectodomain C-terminal domain, using a recombinant human protein...
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating levels of catalytic subunit, presenilin-1 (PS1). Acute treatment SH-SY5Y cells with GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel increases other subunits nicastrin, presenilin enhancer 2,...