A5088294950- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Melanoma and MAPK Pathways
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell death mechanisms and regulation
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Computational Drug Discovery Methods
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Prion Diseases and Protein Misfolding
- Ubiquitin and proteasome pathways
- FOXO transcription factor regulation
- 14-3-3 protein interactions
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- Plant-based Medicinal Research
- Neurological diseases and metabolism
- Drug-Induced Hepatotoxicity and Protection
- Ion channel regulation and function
- Vestibular and auditory disorders
University of Milan
2016-2025
Mario Negri Institute for Pharmacological Research
2014-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2024
Pharmac
2021
Istituto Nazionale di Fisica Nucleare, Sezione di Milano
2013
University of Lausanne
2002-2008
Goethe University Frankfurt
2006
Institute of Neurobiology and Molecular Medicine
1998-1999
University of Turin
1992-1994
Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement c-Jun N-terminal kinase (JNK) in produced by spinal nerve ligation (SNL) (L5). SNL induced slow (>3 d) and persistent (>21 activation JNK, particular JNK1, GFAP-expressing astrocytes cord. In contrast, p38 mitogen-activated protein was found microglia after SNL, which had fallen to near basal level 21 d. Intrathecal infusion JNK peptide inhibitor, D-JNKI-1, did not affect normal responses...
Inability to form new memories is an early clinical sign of Alzheimer’s disease (AD). There ample evidence that the amyloid-β (Aβ) peptide plays a key role in pathogenesis this disorder. Soluble, bio-derived oligomers Aβ are proposed as mediators synaptic and cognitive dysfunction, but more tractable models Aβ−mediated impairment needed. Here we report that, mice, acute intracerebroventricular injections synthetic 1–42 impaired consolidation long-term recognition memory, whereas mature...
Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting requires of a sufficient number islets, usually requiring two or more donors. During the isolation process and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival ultimately contribute graft failure. Here, we have mapped major intracellular stress-signaling pathways mediate human loss during cytokine attack....
A hallmark of Alzheimer disease (AD) is the accumulation amyloid-β (Aβ) peptide in brain. Considerable evidence suggests that soluble Aβ oligomers are responsible for synaptic dysfunction and cognitive deficit observed AD. However, mechanism by which these exert their neurotoxic effect remains unknown. Recently, it was reported bind to cellular prion protein with high affinity. Here, we show N1, main physiological cleavage fragment protein, necessary sufficient binding early oligomeric...
Alzheimer's disease (AD) is a major clinical concern, and the search for new molecules to combat progression remains important. One of hallmarks in AD pathogenesis hyperphosphorylation tau subsequent formation neuro
Altered synaptic function is considered one of the first features Alzheimer disease (AD). Currently, no treatment available to prevent dysfunction excitatory synapses in AD. Identification key modulators synaptopathy particular significance We here characterized pathways leading TgCRND8 mice and showed that c-Jun N-terminal kinase (JNK) activated at spine prior onset cognitive impairment. The specific inhibition JNK, with its inhibiting peptide D-JNKI1, prevented mice. D-JNKI1 avoided both...
Abstract Acute excitotoxic neuronal death was studied in rat organotypic hippocampal slices exposed to 100 µ m N ‐methyl‐ d ‐aspartate. Fulgurant of pyramidal neurons occurred the CA1 and CA3 regions already detectable within 2 h N‐methyl‐ ‐aspartate administration. Morphologically, neither apoptotic nor necrotic but had hallmarks autophagic death, as shown by acid phosphatase histochemistry both electron microscopy CA1. The dying also manifested strong endocytosis horseradish peroxidase or...
Alzheimer disease (AD) is characterized by cognitive impairment that starts with memory loss to end in dementia. Loss of synapses and synaptic dysfunction are closely associated AD patients. Biochemical pathological evidence suggests soluble Aβ oligomers correlate impairment. Here, we used the TgCRND8 mouse model investigate role JNK long term deficits. mice were chronically treated cell-penetrating c-Jun N-terminal kinase inhibitor peptide (D-JNKI1). D-JNKI1, preventing action, completely...
We describe here an innovative, non-transgenic animal model of Alzheimer's disease. This mimics early stages sporadic disease, which represents the vast majority cases. The was obtained by interfering with complex between a disintegrin and metalloproteinase domain containing protein 10 (ADAM10), main α-secretase candidate, its partner, synapse-associated 97, postsynaptic density-membrane associated guanylate kinase family. Association ADAM10 97 governs enzyme trafficking activity at...
Background Oxidative stress is a key feature in the pathogenesis of several neurological disorders. Following oxidative stimuli wide range pathways are activated and contribute to cellular death. The mechanism that couples c-Jun N-terminal kinase (JNK) signaling, pathway conditions, small ubiquitin-related modifier (SUMO), an emerging protein field, largely unknown. Methodology/Principal Findings With this study we investigated if SUMOylation participates regulation JNK activation as well...
<title>Abstract</title> Mutations in DJ-1 cause autosomal recessive Parkinson’s disease. Several functions have been attributed to DJ-1, including a key role the protection from oxidative stress, however how this protein contributes PD pathogenesis is still unclear. Recently, has identified at higher concentration extracellular vesicles (EV) biological fluids of patients, providing link between EV and associated with PD. were isolated medium control rotenone-treated wild-type KO...
Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). plays a role protection from oxidative stress, but how it functions as an "upstream" stress sensor and whether this relates to PD is still unclear. Intriguingly, may act RNA binding protein associating specific mRNA transcripts human brain. Moreover, we previously reported that yeast homolog Hsp31 localizes granules (SGs) after glucose starvation, suggesting for dynamics. Here,...
Abstract Prion diseases are rare neurodegenerative conditions associated with the conformational conversion of cellular prion protein (PrP C ) into PrP Sc , a self-replicating isoform (prion) that accumulates in central nervous system affected individuals. The structure is poorly defined and likely to be heterogeneous, as suggested by existence different strains. latter represents relevant problem for therapy diseases, some potent anti-prion compounds have shown strain-specificity. Designing...