A5021299206- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Lysosomal Storage Disorders Research
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
- Plant Gene Expression Analysis
- Magnesium Alloys: Properties and Applications
- Nerve injury and regeneration
- 14-3-3 protein interactions
- Nuclear Structure and Function
- Corrosion Behavior and Inhibition
- Fungal and yeast genetics research
- Muscle Physiology and Disorders
- Signaling Pathways in Disease
- Tropical and Extratropical Cyclones Research
- Photosynthetic Processes and Mechanisms
- Protein Degradation and Inhibitors
- Phytochemistry and biological activities of Ficus species
- Banana Cultivation and Research
- Neurological diseases and metabolism
- Skin and Cellular Biology Research
- Protein Tyrosine Phosphatases
- RNA regulation and disease
University of Reading
2017-2024
University of Padua
2008-2024
Lrrk2, a gene linked to Parkinson's disease, encodes large scaffolding protein with kinase and GTPase activities implicated in vesicle cytoskeletal-related processes. At the presynaptic site, LRRK2 associates synaptic vesicles through interaction panel of proteins. Here, we show that activity influences dynamics fusion. We therefore investigated whether phosphorylates component(s) exo/endocytosis machinery. have previously observed interacts NSF, hexameric AAA+ ATPase couples ATP hydrolysis...
Abstract Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies experimental models and postmortem PD patients underlined increasing levels dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL shown to covalently modify presynaptic protein αSynuclein (αSyn), whose misfolding aggregation represent a major trait pathology, triggering αSyn...
Mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD) and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of health and incompletely understood, robust evidence indicates that PD-associated mutations alter GTPase activities consequent deregulation downstream signaling pathways. We have previously demonstrated one binding partner P21 (RAC1) Activated Kinase 6 (PAK6). Here,...
Mutations in LRRK2 cause familial Parkinson’s disease and common variants increase risk. kinase activity cellular localization are tightly regulated by phosphorylation of key residues, primarily Ser1292 Ser935, which impacts downstream its substrates, among Rab10. A comprehensive characterization brain as a function age mutations is missing. Here, we monitored Ser935 midbrain, striatum, cortex 1, 6, 12 months-old mice carrying G2019S R1441C or murine bacterial artificial chromosome...
Magnesium alloys have been widely studied as materials for temporary implants, but their use has limited by corrosion rate. Recently, coatings proven to provide an effective barrier. Though only little explored in the field, Atomic Layer Deposition (ALD) stands out a coating technology due outstanding film conformality and density achievable. Here, we first insights into behavior induced biological response of 100 nm thick ALD TiO2, HfO2 ZrO2 on AZ31 alloy means potentiodynamic polarization...
Leucine-rich repeat kinase 2 (LRRK2) is a involved in different cellular functions, including autophagy, endolysosomal pathways, and immune function. Mutations LRRK2 cause autosomal-dominant forms of Parkinson's disease (PD). Heterozygous mutations GBA1, the gene encoding lysosomal enzyme glucocerebrosidase (GCase), are most common genetic risk factors for PD. Moreover, GCase function altered idiopathic PD other disease. Recent work suggests that activity can regulate However, both positive...
Magnesium alloys are increasingly studied as materials for temporary implants. However, their high corrosion rate and susceptibility to corrosion-assisted cracking phenomena, such stress (SCC), continue prevent mainstream use. Recently, coatings have been considered provide an effective solution these issues researchers focused attention on Atomic Layer Deposition (ALD). ALD stands out a coating technology due the outstanding film conformality density achievable, has shown encouraging...
P21 activated kinase 6 (PAK6) is a serine-threonine with physiological expression enriched in the brain and overexpressed number of human tumors. While role PAK6 cancer cells has been extensively investigated, function context poorly understood. Our previous work uncovered link between Parkinson's disease (PD)-associated LRRK2, controlling LRRK2 activity subcellular localization via phosphorylation 14-3-3 proteins. Here, to gain more insights into function, we performed protein-protein...
Abstract Alterations in the dopamine catabolic pathway are known to contribute degeneration of nigrostriatal neurons Parkinson’s disease (PD). The progressive cellular buildup highly reactive intermediate 3,4-dihydroxyphenylacetaldehye (DOPAL) generates protein cross-linking, oligomerization PD-linked αSynuclein (αSyn) and imbalance quality control. In this scenario, autophagic cargo sequestome-1 (SQSTM1/p62) emerges as a target DOPAL-dependent accumulation cytosolic clusters. Although...
Leucine Rich Repeat Kinase 2 (LRRK2) is a multidomain enzyme with dual kinase and GTPase activities. Following the identification of mutations in LRRK2 gene linked to familial Parkinson’s disea...
Mutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through formation a coat-like complex and its loss function results lysosomal axonal transport impairments. However, upstream mechanisms regulate trafficking are unknown. Here, using proteomics CRISPR/Cas9-mediated tagging endogenous we identified subset 14-3-3...
P21 activated kinase 6 (PAK6) is a serine-threonine with physiological expression enriched in the brain and overexpressed number of human tumors. While role PAK6 cancer cells has been extensively investigated, function context poorly understood. Our previous work uncovered link between Parkinson's disease (PD)-associated LRRK2, controlling LRRK2 activity subcellular localization via phosphorylation 14-3-3 proteins. Here, to gain more insights into function, we performed protein-protein...
<title>Abstract</title> P21 activated kinase 6 (PAK6) is a serine-threonine with physiological expression enriched in the brain and overexpressed number of human tumors. While role PAK6 cancer cells has been extensively investigated, function context poorly understood. Our previous work uncovered link between Parkinson’s disease (PD)-associated LRRK2, controlling LRRK2 activity subcellular localization <italic>via</italic> phosphorylation 14-3-3 proteins. Here, to gain more insights into...
Autophagy is a highly conserved homeostatic process essential for the bulk degradation of cytoplasmic components and aggregated proteins. Multiple evidence indicates that impairment (macro)autophagy leads to neurodegeneration, such as Parkinson disease (PD). Our previous work showed p21 activated kinase 6 (PAK6) interacts with PD-associated leucine-rich repeat (LRRK2) promote neurite outgrowth in mouse striatum; still function PAK6 brain largely unknown. Here, we found downregulation...
Abstract Dopamine dyshomeostasis has been acknowledged to be among the determinants of nigrostriatal neuron degeneration in Parkinson’s disease (PD). Several studies experimental models and postmortem PD patients underlined increasing levels aldehydic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL shown covalently modify presynaptic protein αSynuclein (αSyn), whose misfolding aggregation represent a major trait pathology,...
Abstract LRRK2 is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways and vesicle trafficking. Mutations cause autosomal dominant forms of Parkinson’s disease (PD). Heterozygous mutations GBA1 , the gene encoding lysosomal enzyme glucocerebrosidase (GCase), are most common genetic risk factors for PD. Moreover, GCase function altered idiopathic PD other disease. Recent work suggests that activity can regulate function. However, both positive...
Abstract Mutations in SPG11 , encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through formation a coat-like complex and its loss function results lysosomal axonal transport impairments. However, upstream mechanisms regulate trafficking are unknown. Here, using proteomics CRISPR/Cas9-mediated tagging endogenous we identified...