Hyaluronic acid-based hydrogels modulate neuroinflammation and extracellular matrix remodelling in multiple sclerosis: insights from a primary cortical cell model.

Multiple sclerosis (MS) is the main neurodegenerative disorder among young adults. Cortical involvement in MS has emerged as an important determinant of disease progression. Although inflammation is recognized as a key feature, the mechanisms of cortical pathology are still poorly understood.

Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

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 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.

Tagless LysoIP for immunoaffinity enrichment of native lysosomes from clinical samples.

Lysosomes are implicated in a wide spectrum of human diseases, including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration, and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.

Prodromal Parkinson's disease and the catecholaldehyde hypothesis: Insight from olfactory bulb organotypic cultures.

Parkinson's disease (PD) is a progressive, neurodegenerative disorder with an increasing incidence, unknown etiology, and is currently incurable. Advances in understanding the pathological mechanisms at a molecular level have been slow, with little attention focused on the early prodromal phase of the disease. Consequently, the development of early-acting disease-modifying therapies has been hindered.

Micromotion Derived Fluid Shear Stress Mediates Peri-Electrode Gliosis through Mechanosensitive Ion Channels.

The development of bioelectronic neural implant technologies has advanced significantly over the past 5 years, particularly in brain-machine interfaces and electronic medicine. However, neuroelectrode-based therapies require invasive neurosurgery and can subject neural tissues to micromotion-induced mechanical shear, leading to chronic inflammation, the formation of a peri-electrode void and the deposition of reactive glial scar tissue. These structures act as physical barriers, hindering electrical signal propagation and reducing neural implant functionality.

Role of Autophagy Pathway in Parkinson's Disease and Related Genetic Neurological Disorders.

The elucidation of the function of the PINK1 protein kinase and Parkin ubiquitin E3 ligase in the elimination of damaged mitochondria by autophagy (mitophagy) has provided unprecedented understanding of the mechanistic pathways underlying Parkinson's disease (PD). We provide a comprehensive overview of the general importance of autophagy in Parkinson's disease and related disorders of the central nervous system. This reveals a critical link between autophagy and neurodegenerative and neurodevelopmental disorders and suggests that strategies to modulate mitophagy may have greater relevance in the CNS beyond PD.

Golgi-IP, a tool for multimodal analysis of Golgi molecular content.

The Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signaling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease.

Dysregulation of astrocytic mitochondrial function following exposure to a dopamine metabolite: Implications for Parkinson's disease.

The monoamine oxidase metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde (DOPAL), is hypothesized to induce neurodegeneration in Parkinson's disease (PD). However, DOPAL's effect on astrocyte function is less well known. Furthermore, the conflicting protective and pathological roles of resting and reactive astrocytes in Parkinson's disease have led to astrocytes being characterized as a double-edged sword in this disease.

Mitral cells and the glucagon-like peptide 1 receptor: The sweet smell of success?

The olfactory bulb (OB) is often affected at very early stages of neurodegenerative disorders, in the so-called "prodromal" phase. In Parkinson's disease (PD), olfactory disturbances appear years before motor symptoms arise. Additionally, pathological alpha-synuclein aggregates are found in olfactory regions before spreading to other areas of the brain.

Image-Based Tracking of Anticancer Drug-Loaded Nanoengineered Polyelectrolyte Capsules in Cellular Environments Using a Fast Benchtop Mid-Infrared (MIR) Microscope.

Drug delivery monitoring and tracking in the human body are two of the biggest challenges in targeted therapy to be addressed by nanomedicine. The ability of imaging drugs and micro-/nanoengineered drug carriers and of visualizing their interactions at the cellular interface in a label-free manner is crucial in providing the ability of tracking their cellular pathways and will help understand their biological impact, allowing thus to improve the therapeutic efficacy. We present a fast, label-free technique to achieve high-resolution imaging at the mid-infrared (MIR) spectrum that provides chemical information.