Track topics on Twitter Track topics that are important to you
Highly toxic protein misfolded oligomers associated with neurological disorders such as Alzheimer's and Parkinson's diseases are nowadays considered primarily responsible for promoting synaptic failure and neuronal death. Unraveling the relationship between structure and neurotoxicity of protein oligomers appears pivotal in understanding the causes of the pathological process, as well as in designing novel diagnostic and therapeutic strategies tuned toward the earliest and presymptomatic stages of the disease. Here, it is benefited from tip-enhanced Raman spectroscopy (TERS) as a surface-sensitive tool with spatial resolution on the nanoscale, to inspect the spatial organization and surface character of individual protein oligomers from two samples formed by the same polypeptide sequence and different toxicity levels. TERS provides direct assignment of specific amino acid residues that are exposed to a large extent on the surface of toxic species and buried in nontoxic oligomers. These residues, thanks to their outward disposition, might represent structural factors driving the pathogenic behavior exhibited by protein misfolded oligomers, including affecting cell membrane integrity and specific signaling pathways in neurodegenerative conditions.
This article was published in the following journal.
Name: Small (Weinheim an der Bergstrasse, Germany)
We have studied two misfolded oligomeric forms of the protein HypF-N, which show similar morphologies but very different toxicities. We measured over 80 intermolecular distance-dependent parameters fo...
The deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. It is...
Oligomers populated during the early amyloid aggregation process are more toxic than mature fibrils, but pinpointing the exact toxic species among highly dynamic and heterogeneous aggregation intermed...
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder affecting millions of people worldwide. Therefore, finding effective interventions and therapies is extremely importa...
Mutations in Cu/Zn-superoxide dismutase (SOD1) gene are linked to 10-20% of familial amyotrophic lateral sclerosis (fALS) cases. The mutations cause misfolding and self-assembly of SOD1 into toxic oli...
This study measures circulating, misfolded ATTR oligomers in asymptomatic ATTRm amyloidosis genetic carriers longitudinally over five years.
The trials in this protocol deals with the effect of pretreatment with rhTSH on radioiodine treatment of thyroid size and function, in patients with nontoxic and toxic nodular goiter. It i...
The objective of this cross-sectional study is to assess the prevalence of depression at 2 months, 6 months, and 1 year postpartum in women who had an immediate postpartum hemorrhage (imme...
Gaucher disease is a lysosomal storage disorder resulting from a deficiency in the key enzyme beta-glucocerebrosidase (GCase). The enzyme deficiency is caused by genetic mutations, which c...
A cochlear implant is a device for the rehabilitation of severe to profound hearing loss. Despite the standardization of surgical procedures and rehabilitation, speech discrimination perfo...
Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.
Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.
An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.
A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...