Dario R. Alessi
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View article: Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human Open
Our understanding of how the body communicates with the brain to coordinate their functions is remarkably limited. At the blood-brain barrier (BBB), brain endothelial cells (BECs) are ideally positioned to mediate signaling between blood a…
View article: Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved peptide motif
Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved peptide motif Open
Inherited mutations in VPS35 and LRRK2 kinase lead to hyperphosphorylation of Rab GTPases. RH2 domain-containing proteins from the RILP homology family, such as RILPL1, are Rab effectors that recognize the LRRK2-phosphorylated switch 2 thr…
View article: Reinventing Chemiluminescence through Redox-Driven Self-Assembly
Reinventing Chemiluminescence through Redox-Driven Self-Assembly Open
Chemiluminescence (CL) typically derives from harvesting the energy released during the cleavage of covalent bonds, wherein molecular substrates are irreversibly consumed to generate electronically excited states. In contrast, regenerative…
View article: Alternate Splicing Directs PMCA2 to Lysosomes and is Linked to Neurodegeneration
Alternate Splicing Directs PMCA2 to Lysosomes and is Linked to Neurodegeneration Open
Plasma membrane calcium ATPase (PMCAs) are believed to function exclusively at the plasma membrane where they expel calcium from the cytosol. We have unexpectedly identified a splice variant-dependent localisation of the PMCA isoform PMCA2…
View article: Precision Stratification: Kinase Assay in Asian <i>LRRK2</i> Risk Carriers and Idiopathic Parkinson Disease
Precision Stratification: Kinase Assay in Asian <i>LRRK2</i> Risk Carriers and Idiopathic Parkinson Disease Open
Importance LRRK2 kinase inhibition is one of the most promising therapeutic strategies in Parkinson’s disease (PD), yet understanding of kinase activity in the Asian-prevalent p.G2385R and p.R1628P variants, each affecting 5–10% of PD pati…
View article: Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons
Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons Open
The end-stage pathology of Parkinson's disease (PD) involves the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). However, synaptic deregulation of these neurons begins much earlier. Understanding the mechani…
View article: Dynamic Reconfiguration of Pt(II) Supramolecular Assemblies via Ligand Exchange
Dynamic Reconfiguration of Pt(II) Supramolecular Assemblies via Ligand Exchange Open
Supramolecular chemistry enables molecules to dynamically adapt and reorganize in response to their environment, providing a key route to achieving high levels of structural and functional complexity. This work explores a particular strate…
View article: TDP-43 loss of function drives aberrant splicing in Parkinson’s disease
TDP-43 loss of function drives aberrant splicing in Parkinson’s disease Open
Introductory paragraph While mRNA splicing dysregulation is a well-established contributor to neurodegeneration in disorders such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), its role in Parkinson’s disease (PD…
View article: Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons
Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons Open
The end-stage pathology of Parkinson's disease (PD) involves the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). However, synaptic deregulation of these neurons begins much earlier. Understanding the mechani…
View article: Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved TBM motif
Structural basis for binding of RILPL1 to TMEM55B reveals a lysosomal platform for adaptor assembly through a conserved TBM motif Open
SUMMARY Inherited mutations in VPS35 and the kinase LRRK2 lead to hyperphosphorylation of Rab GTPases and promote the formation of phospho-Rab signalling complexes. A subset of RH2 domain-containing proteins from the RILP-homology family, …
View article: Generation of HEK293 TMEM55B and TMEM55A CRISPR/Cas9 double knock-out cell line v1
Generation of HEK293 TMEM55B and TMEM55A CRISPR/Cas9 double knock-out cell line v1 Open
The protocol described the strategy taken for knocking out TMEM55A and TMEM55B gene in HEK293 cells uisng CRISPR-Cas9 method.
View article: Functional and Structural Characterization of <scp>LRRK2</scp> p. <scp>V1447L</scp> in Parkinson's Disease
Functional and Structural Characterization of <span>LRRK2</span> p. <span>V1447L</span> in Parkinson's Disease Open
Background Gain‐of‐kinase‐function variants in LRRK2 are a leading cause of monogenic Parkinson's disease (PD). Objectives We tested the functional impact of a novel LRRK2 variant p.V1447L identified in a young‐onset PD patient in vivo in …
View article: NRBP1 and TSC22D proteins affect distal convoluted tubule physiology through modulation of the WNK pathway
NRBP1 and TSC22D proteins affect distal convoluted tubule physiology through modulation of the WNK pathway Open
The with-no-lysine (K) (WNK) kinases regulate processes such as cell volume and epithelial ion transport through the modulation of cation chloride cotransporters such as the NaCl cotransporter (NCC) present in the distal convoluted tubule …
View article: NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress
NRBP1 pseudokinase binds to and activates the WNK pathway in response to osmotic stress Open
WNK family kinases are regulated by osmotic stress and control ion homeostasis by activating SPAK and OXSR1 kinases. Using a proximity labeling approach, we found that osmotic stress promotes the association of WNK1 with the NRBP1 pseudoki…
View article: Proteomics Sample Preparation for Affinity-Purification Mass Spectrometry v1
Proteomics Sample Preparation for Affinity-Purification Mass Spectrometry v1 Open
Protocol for the preparation of immunoprecipitated protein samples captured via magnetic bead technologies, for affinity-purification mass spectrometry analysis.
View article: FLAG-tag mediated co-immunoprecipitation of phosphorylated Rab GTPases with cellular interacting proteins v1
FLAG-tag mediated co-immunoprecipitation of phosphorylated Rab GTPases with cellular interacting proteins v1 Open
Leucine Rich Repeat Kinase 2 phosphorylates a subset of Rab GTPases at a conserved Ser/Thr residue in their switch 2 region. This modification disrupts interactions between Rabs and effectors/regulators while enabling binding to novel phos…
View article: FLAG-tag mediated co-immunoprecipitation of phosphorylated Rab GTPases with cellular interacting proteins v2
FLAG-tag mediated co-immunoprecipitation of phosphorylated Rab GTPases with cellular interacting proteins v2 Open
Leucine Rich Repeat Kinase 2 phosphorylates a subset of Rab GTPases at a conserved Ser/Thr residue in their switch 2 region. This modification disrupts interactions between Rabs and effectors/regulators while enabling binding to novel phos…
View article: <i>C9orf72</i>polyGA knock-in mice exhibit mild motor and proteomic changes consistent with ALS/FTD
<i>C9orf72</i>polyGA knock-in mice exhibit mild motor and proteomic changes consistent with ALS/FTD Open
A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion is translated into five different dipeptide repeat proteins: polyGA, polyG…
View article: Dynamic Reconfiguration of Pt(II) Supramolecular Assemblies via Ligand Exchange
Dynamic Reconfiguration of Pt(II) Supramolecular Assemblies via Ligand Exchange Open
Supramolecular chemistry enables molecules to dynamically adapt and reorganize in response to their environment, providing a key route to achieving high levels of structural and functional complexity. This work explores a novel strategy fo…
View article: Inflammation and IL-4 regulate Parkinson’s and Crohn’s disease associated kinase LRRK2
Inflammation and IL-4 regulate Parkinson’s and Crohn’s disease associated kinase LRRK2 Open
Mutations in Leucine-Rich Repeat protein Kinase 2 (LRRK2) are associated with Parkinson’s disease (PD) and Crohn’s disease (CD), but the regulation of LRRK2 during inflammation remains relatively unexplored. Here we describe the developmen…
View article: Functional and Structural Characterization of LRRK2 p.V1447L in Parkinson’s Disease
Functional and Structural Characterization of LRRK2 p.V1447L in Parkinson’s Disease Open
Background Gain-of-kinase-function variants in LRRK2 are a leading cause for Parkinson’s disease (PD). Objectives We tested the functional impact of a novel LRRK2 variant p.V1447L identified in a young onset PD patient in vivo in periphera…
View article: PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease
PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease Open
Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of Rab GTPases that regulate receptor trafficking; activating mutations in LRRK2 are linked to Parkinson’s disease. Rab phosphorylation is a transient event that can be reversed …
View article: Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain
Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain Open
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson’s disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 …