A5016273259- Extracellular vesicles in disease
- Alzheimer's disease research and treatments
- RNA Interference and Gene Delivery
- Prion Diseases and Protein Misfolding
- MicroRNA in disease regulation
- interferon and immune responses
- Virus-based gene therapy research
- Neurological diseases and metabolism
- CRISPR and Genetic Engineering
- Advanced Neuroimaging Techniques and Applications
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Down syndrome and intellectual disability research
- Genetic Neurodegenerative Diseases
- Nuclear Receptors and Signaling
- RNA Research and Splicing
- Nerve injury and regeneration
- Endoplasmic Reticulum Stress and Disease
- Advanced Nanomaterials in Catalysis
- Connective tissue disorders research
- Peptidase Inhibition and Analysis
- Particle accelerators and beam dynamics
- Neurological Disorders and Treatments
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neural Engineering
Indiana University – Purdue University Indianapolis
2021-2024
Indiana University School of Medicine
2021-2024
Universidad de Los Andes
2023
Universidad de Los Andes, Chile
2016-2023
University of Antofagasta
2014-2021
Abstract Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and regarding the structure of amyloid-β (Aβ) tau filaments unknown. Here we report Aβ from two brains. We found 40 (types IIIa IIIb) that differ those previously reported sporadic types 42 (I II) identical to familial AD. Tau (paired helical straight filaments) were AD, supporting notion common mechanism through which amyloids trigger aggregation tau. This...
Astrocytes use gliotransmitters to modulate neuronal function and plasticity. However, the role of small extracellular vesicles, called exosomes, in astrocyte-to-neuron signaling is mostly unknown. Exosomes originate multivesicular bodies parent cells are secreted by fusion body limiting membrane with plasma membrane. Their molecular cargo, consisting RNA species, proteins, lipids, part cell type state specific. Among species transported microRNAs (miRNAs) able modify gene expression...
Abstract In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, ordered cores filaments adopt distinct folds. Here, we analyze isolated from brain individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) a nonsense mutation in PRNP gene that leads to early termination translation PrP (Q160Ter or Q160X), and Gerstmann–Sträussler–Scheinker (GSS) disease, missense an amino acid substitution at residue 198 (F198S) PrP. The clinical...
Prion protein (PrP) aggregation and formation of PrP amyloid (APrP) are central events in the pathogenesis prion diseases. In dominantly inherited amyloidosis known as Gerstmann-Sträussler-Scheinker (GSS) disease, plaques made present throughout brain. The c.593t > c mutation gene (PRNP) results a phenylalanine to serine amino acid substitution at residue 198 (F198S) causes most severe among GSS variants. It has been shown that neurodegeneration this disease is associated with presence...
In the last few decades, it has been established that astrocytes play key roles in regulation of neuronal morphology. However, contribution astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation neurons only recently addressed. Here, we showed cultured expressing a GFP-tagged version stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release are transferred into hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs C-GFP sEVs) displayed an...
In the last decades, it has been established that astrocytes play key roles in regulation of neuronal morphology. However, contribution astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation neurons only recently addressed. Here, we showed cultured expressing a GFP tagged version stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release which are transferred into hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs C-GFP sEVs) displayed an...
Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) that lack an amyloid core recognizable, but not fluorescent, Thioflavin S (ThS) preparations. Amino-terminally truncated post-translationally modified Aβ peptide species main component CWPs. Tau immunopositive neurites may be present In...
Stress is a widespread problem in today's societies, having important consequences on brain function. Among the plethora of mechanisms involved stress response at molecular level, role microRNAs (miRNAs) beginning to be recognized. The control gene expression by these noncoding RNAs makes them essential regulators neuronal and synaptic physiology, alterations their levels have been associated with pathological conditions mental disorders. In particular, excitatory (i.e., glutamate-mediated)...
The Microtubule-Associated Protein Tau (MAPT) is one of the proteins that are central to neurodegenerative diseases. nature intracellular tau aggregates determined by cell types whether neuronal or glial, participating isoforms, and structure amyloid filament. transmembrane protein 106B (TMEM106B) has recently emerged as another significant player in neurodegeneration aging. In nervous system, composition gray white matter differs considerably. consists nerve bodies, dendrites, unmyelinated...
Abstract Background Down syndrome (DS) is the most common and best‐known chromosomal disorder in humans frequent cause of intellectual disability genetic origin, affecting about 6 million people worldwide. Individuals with DS may develop Alzheimer disease (AD) by age 55‐60 years, sometimes as young 40 years due to triplication amyloid β precursor protein (AβPP) gene, which located on chromosome 21. The AD neuropathological phenotype includes amyloid‐β (Aβ) deposition (parenchymal vascular)...
Molecular brain therapies require the development of molecular switches to control gene expression in a limited and regulated manner time space. Light-switchable systems allow precise with an enhanced spatio-temporal resolution compared chemical inducers. In this work, we adapted existing light-switchable Light-On system into lentiviral platform, which consists two modules: (i) one for blue trans-activator GAVPO (ii) second module containing inducible-UAS promoter (UAS) modulated by...
ABSTRACT Recent studies have described a new mechanism of intercellular communication mediated by various types extracellular vesicles (EVs). In particular, exosomes are small EVs (sEVs) released to the environment fusion endosomal pathway-related multivesicular bodies (containing intraluminal vesicles) with plasma membrane. sEVs contain molecular cargo consisting lipids, proteins, and nucleic acids. However, loading mechanisms for this complex not yet been completely elucidated. that line,...
The Apolipoprotein E-ε4 allele (APOE-ε4) is the strongest genetic risk factor for late onset Alzheimer disease (AD). ApoE plays a critical role in amyloid-β (Aβ) accumulation AD, and deletion of murine gene mouse models results decrease or inhibition Aβ deposition. association between presence amyloid amyloidoses suggests more general fibrillogenesis process. However, whether decreasing levels would attenuate pathology different has not been directly addressed. Familial Danish dementia (FDD)...
Abstract Emerging evidence highlights the relevance of protein post-translational modification by SUMO (Small Ubiquitin-like Modifier) in central nervous system for modulating cognition and plasticity health disease. In these processes, astrocyte-to-neuron crosstalk mediated extracellular vesicles (EVs) plays a yet poorly understood role. Small EVs (sEVs), including microvesicles exosomes, contain molecular cargo lipids, proteins, nucleic acids that define their biological effect on target...
Emerging evidence highlights the relevance of protein post-translational modification by SUMO (Small Ubiquitin-like Modifier) in central nervous system for modulating cognition and plasticity health disease. In these processes, astrocyte-to-neuron crosstalk mediated extracellular vesicles (EVs) plays a yet poorly understood role. Small EVs (sEVs), including microvesicles exosomes, contain molecular cargo lipids, proteins, nucleic acids that define their biological effect on target cells....