Search results for "Degeneration"

Peripherin-2 differentially interacts with cone opsins in outer segments of cone photoreceptors

2016

Peripherin-2 is a glycomembrane protein exclusively expressed in the light-sensing compartments of rod and cone photoreceptors designated as outer segments (OS). Mutations in peripherin-2 are associated with degenerative retinal diseases either affecting rod or cone photoreceptors. While peripherin-2 has been extensively studied in rods, there is only little information on its supramolecular organization and function in cones. Recently, we have demonstrated that peripherin-2 interacts with the light detector rhodopsin in OS of rods. It remains unclear, however, if peripherin-2 also binds to cone opsins. Here, using a combination of co-immunoprecipitation analyses, transmission electron micr…

Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology?

2016

Prevention of progression in neurological diseases, particularly in multiple sclerosis (MS) but also in neurodegenerative diseases, remains a significant challenge. MS patients switch from a relapsing-remitting to a progressive disease course, but it is not understood why and how this conversion occurs and why some patients never experience disease progression. Do aging and accumulation of neuronal damage induce progression, or do cognitive symptoms and accelerated grey matter (GM) atrophy point to distinct processes affecting networks? This review weighs accepted dogma against real data on the secondary progressive phase of the disease, highlighting current challenges in this important fie…

The Sigma-1 Receptor at the Crossroad of Proteostasis, Neurodegeneration, and Autophagy.

2020

Neurodegenerative diseases are linked to dysfunctional proteostasis and disturbed autophagy. Here, we discuss how the sigma-1 receptor (Sig-1R) may act at the intersection of this interaction, as loss-of-function mutations of this unique chaperone are associated with defective autophagy and its pharmacological activation induces autophagic activity.

2019

With the rise of Next-Generation-Sequencing (NGS) methods, Micro-RNAs (miRNAs) have achieved an important position in the research landscape and have been found to present valuable diagnostic tools in various diseases such as multiple sclerosis or lung cancer. There is also emerging evidence that miRNAs play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) or Parkinson's disease (PD). Apparently, these diseases come along with changes in miRNA expression patterns which led to attempts from researchers to use these small RNA species from several body fluids for a better diagnosis and in order to observe disease progression. Additionally, it…

Collapsibility of the internal jugular veins in the lateral decubitus body position: A potential protective role of the cerebral venous outflow again…

2019

Recent research has revealed that patients with neurodegenerative disease sleep longer in the supine position, while healthy controls prefer sleeping in the lateral decubitus position. Thus, sleeping in the lateral position seems to be protective against neurodegeneration. It has also been suggested that a protective role of this body position could be associated with better cerebral venous drainage in this body position, which results in more active glymphatic system of the brain (the system responsible for clearance of the cerebral tissue from waste products, e.g. amyloid-β). Since no published evidence exists regarding venous outflow from the cranial cavity in the lateral decubitus posit…

Characterizing microstructural tissue properties in multiple sclerosis with diffusion MRI at 7 T and 3 T: The impact of the experimental design

2019

The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy contr…

Hypothesis: Etiologic and Molecular Mechanistic Leads for Sporadic Neurodegenerative Diseases Based on Experience With Western Pacific ALS/PDC

2019

Seventy years of research on Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia Complex (ALS/PDC) have provided invaluable data on the etiology, molecular pathogenesis and latency of this disappearing, largely environmental neurodegenerative disease. ALS/PDC is linked to genotoxic chemicals (notably methylazoxymethanol, MAM) derived from seed of the cycad plant (Cycas spp.) that were used as a traditional food and/or medicine in all three disease-affected Western Pacific populations. MAM, nitrosamines and hydrazines generate methyl free radicals that damage DNA (in the form of O6-methylguanine lesions) that can induce mutations in cycling cells and degenerative changes …

The Impact of Microbiota on the Pathogenesis of Amyotrophic Lateral Sclerosis and the Possible Benefits of Polyphenols. An Overview

2021

The relationship between gut microbiota and neurodegenerative diseases is becoming clearer. Among said diseases amyotrophic lateral sclerosis (ALS) stands out due to its severity and, as with other chronic pathologies that cause neurodegeneration, gut microbiota could play a fundamental role in its pathogenesis. Therefore, polyphenols could be a therapeutic alternative due to their anti-inflammatory action and probiotic effect. Thus, the objective of our narrative review was to identify those bacteria that could have connection with the mentioned disease (ALS) and to analyze the benefits produced by administering polyphenols. Therefore, an extensive search was carried out selecting the most…

Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis

2020

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron (MN) disease. Its primary cause remains elusive, although a combination of different causal factors cannot be ruled out. There is no cure, and prognosis is poor. Most patients with ALS die due to disease-related complications, such as respiratory failure, within three years of diagnosis. While the underlying mechanisms are unclear, different cell types (microglia, astrocytes, macrophages and T cell subsets) appear to play key roles in the pathophysiology of the disease. Neuroinflammation and oxidative stress pave the way leading to neurodegeneration and MN death. ALS-associated mitochondrial dysfunction occurs at different le…

Functions and Therapeutic Potential of Extracellular Hsp60, Hsp70, and Hsp90 in Neuroinflammatory Disorders

2021

Neuroinflammation is implicated in central nervous system (CNS) diseases, but the molecular mechanisms involved are poorly understood. Progress may be accelerated by developing a comprehensive view of the pathogenesis of CNS disorders, including the immune and the chaperone systems (IS and CS). The latter consists of the molecular chaperones; cochaperones; and chaperone cofactors, interactors, and receptors of an organism and its main collaborators in maintaining protein homeostasis (canonical function) are the ubiquitin–proteasome system and chaperone-mediated autophagy. The CS has also noncanonical functions, for instance, modulation of the IS with induction of proinflammatory cytokines. …