Publications de Maurizio Molinari

A novel allosteric GCase modulator prevents Tau accumulation in GBA1WT and GBA1L444P/L444P cellular models

A slow decline in the autophagy-lysosomal pathway is a hallmark of the normal aging brain. Yet, an acceleration of this cellular function may propel neurodegenerative events. In fact, mutations in genes associated with the autophagy-lysosomal pathway can l ...

Springer Science and Business Media LLC2025

The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux

Maurizio Molinari

Organellophagy receptors control the generation and delivery of portions of their homing organelle to acidic degradative compartments to recycle nutrients, remove toxic or aged macromolecules and remodel the organelle upon physiologic or pathologic cues. H ...

2025

Allosteric Modulation of GCase Enhances Lysosomal Activity and Reduces ER Stress in GCase-Related Disorders

Maurizio Molinari

Variants in the GBA1 gene, encoding the lysosomal enzyme glucosylceramidase beta 1 (GCase), are linked to Parkinson’s disease (PD) and Gaucher disease (GD). Heterozygous variants increase PD risk, while homozygous variants lead to GD, a lysosomal storage d ...

MDPI AG2025

ER remodelling by ER-phagy in neurogenesis

Maurizio Molinari

The endoplasmic reticulum (ER) controls the synthesis of lipids and proteins and Ca2+ homeostasis, as well as contacting other organelles and the plasma membrane. A study now looks at a process by which this compartment is remodelled in axons during neurog ...

NATURE PORTFOLIO2024

TMX5/TXNDC15, a natural trapping mutant of the PDI family is a client of the proteostatic factor ERp44

Maurizio Molinari

The ER is the organelle of nucleated cells that produces lipids, sugars, and proteins. More than 20 ER-resident members of the protein disulfide isomerase (PDI) family regulate formation, isomerization, and disassembly of covalent bonds in newly synthesize ...

LIFE SCIENCE ALLIANCE LLC2024

Rescue of secretion of rare-disease-associated misfolded mutant glycoproteins in UGGT1 knock-out mammalian cells

Maurizio Molinari

Endoplasmic reticulum (ER) retention of misfolded glycoproteins is mediated by the ER-localized eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognizes a misfolded glycoprotein and flags it ...

Wiley2024

ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction

Maurizio Molinari

The endoplasmic reticulum (ER) produces proteins destined to organelles of the endocytic and secretory pathways, the plasma membrane, and the extracellular space. While native proteins are transported to their intra- or extracellular site of activity, fold ...

Springernature2024

Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes

Maurizio Molinari

Lysosomal compartments control the clearance of cell-own material (autophagy) or of material that cells endocytose from the external environment (heterophagy) to warrant supply of nutrients, to eliminate macromolecules or parts of organelles present in exc ...

WILEY2024

Control of nuclear envelope dynamics during acute ER stress by LINC complexes disassembly and selective, asymmetric autophagy of the outer nuclear membrane

Maurizio Molinari

The endoplasmic reticulum (ER) extends to the outer (ONM) and the inner (INM) nuclear membrane forming the nuclear envelope (NE) that delimits the nucleoplasm containing the cell genome. Unfolded protein responses (UPRs) and reticulophagy responses increas ...

Taylor & Francis Inc2024

Tau accumulation in degradative organelles is associated to lysosomal stress

Maurizio Molinari

Neurodegenerative disorders are characterized by the brain deposition of insoluble amyloidogenic proteins, such as alpha-synuclein or Tau, and the concomitant deterioration of cell functions such as the autophagy-lysosomal pathway (ALP). The ALP is involve ...

Nature Portfolio2023