Breaking News
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
February 22, 2019 - Researchers uncover biochemical pathway that may help identify drugs to treat Alzheimer’s
February 22, 2019 - Biologist uses new grant to find ways to eliminate schistosomiasis
February 22, 2019 - Bag-mask ventilation to help patients breathe during intubation prevents complications
February 22, 2019 - AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis
February 22, 2019 - Nature versus nurture and addiction
February 22, 2019 - New website connects researchers with data experts, resources | News Center
February 22, 2019 - Today’s Concerns About Drug Prices Echo The Past
February 22, 2019 - CT and Doppler equipment have low accuracy in detecting cerebral vasospasm and ischemia
February 22, 2019 - Study finds out similarity in function between healthy retina cell and tumor cell
February 22, 2019 - CWRU awarded NIH grant to identify effective treatments for intimate partner violence
February 22, 2019 - Oncotype DX Not Cost-Effective for Low-Risk Breast Cancer
February 22, 2019 - Scientists discover new type of immune cells that are essential for forming heart valves
February 22, 2019 - Talk About Déjà Vu: Senators Set To Re-Enact Drug Price Hearing Of 60 Years Ago
February 22, 2019 - Genetic defect linked to pediatric liver disease identified
February 22, 2019 - New cellular atlas could provide a deeper insight into blinding diseases
February 22, 2019 - Growing number of cancer survivors, fewer providers point to challenge in meeting care needs
February 22, 2019 - Innovative compound offers a new therapeutic approach to treat multiple sclerosis
February 22, 2019 - $1.5 million grant to develop opioid treatment program for jail detainees
February 22, 2019 - FDA’s new proposed rule would update regulatory requirements for sunscreen products in the U.S
February 22, 2019 - Most Hip, Knee Replacements Last Decades, Study Finds
February 22, 2019 - Wellness problems prevalent among ob-gyn residents
February 22, 2019 - In the Spotlight: “The world is your oyster in geriatrics”
February 22, 2019 - Successful testing of multi-organ “human-on-a-chip” could replace animals as test subjects
February 22, 2019 - Analysis of cervical precancer shows decline in two strains of HPV
February 22, 2019 - Sugary stent eases suturing of blood vessels
February 22, 2019 - From surgery to psychiatry: A medical student reevaluates his motivations
February 22, 2019 - Is New App From Feds Your Answer To Navigating Medicare Coverage? Yes And No
February 22, 2019 - New pacemakers powered by heartbeats could reduce need for surgery
February 22, 2019 - The United States records highest drug overdose death rates
February 22, 2019 - Phase 1 data reinforce safety profile of new drug for treating Duchenne muscular dystrophy
February 22, 2019 - Vitamin D supplementation less effective in the presence of obesity, shows study
February 22, 2019 - Novostia raises CHF 6.5 million to advance its aortic, mitral heart valve to clinical trials
February 22, 2019 - CPRIT awards nearly $20 million to The University of Texas MD Anderson Cancer Center
February 22, 2019 - Sarepta Announces FDA Acceptance of Golodirsen (SRP-4053) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 53
February 22, 2019 - An institutional effort to reduce the amount of opioids prescribed following lumbar surgery
February 22, 2019 - Family-history-based models perform better than non-family-history based models
February 22, 2019 - Failure to take statins leads to higher mortality rates | News Center
February 22, 2019 - New study explains why some patients report phantom sensations after limb amputation
February 22, 2019 - First motor-controlled heart valves implanted by Mainz University Medical Center
February 22, 2019 - Novel preclinical model mimics persistent interneuron loss seen in preterm infants
February 22, 2019 - Global health burden of glaucoma has increased, study reveals
February 22, 2019 - A holistic approach key to minimize treatment complexity in patients with interstitial lung disease
February 22, 2019 - 1 in 10 middle-aged Chinese adults are at high risk for heart disease, finds study
February 22, 2019 - More than half a million breast cancer patient’s lives saved by improvements in treatment
February 22, 2019 - Study finds no evidence that tougher policies prevent teenage cannabis use
February 22, 2019 - New blood test detects genetic disorders in fetuses
February 22, 2019 - Lower Self-Perception Observed in Children With Amblyopia
February 22, 2019 - Up to 15 percent of children have sleep apnea, yet 90 percent go undiagnosed
February 22, 2019 - Rare pulmonary defect prompts parents’ nationwide search for answers | News Center
February 22, 2019 - Lesbian and bisexual women at greater risk of being overweight, study finds
February 22, 2019 - UQ research may explain why vitamin D is essential for brain health
February 22, 2019 - Heart Attacks Rising Among Younger Women
February 22, 2019 - How your smartphone is affecting your relationship
February 22, 2019 - Orthopaedic surgeon receives prestigious award, $10 million grant | News Center
February 22, 2019 - New sepsis test could save thousands of lives
February 22, 2019 - Cervical cancer could be eradicated by 2100
February 21, 2019 - Sustained smoking cessation can lower risk of seropositive RA
February 21, 2019 - Thousands with chronic UTIs are not receiving the treatment they need
February 21, 2019 - Are teens getting high on social media? The surprising study seeking the pot-Instagram link
February 21, 2019 - Stanford expands biobank services | News Center
February 21, 2019 - Scientists identify link between drinking contexts and early onset intoxication among adolescents
February 21, 2019 - Strong social support may reduce cardiovascular disease risk in postmenopausal women
February 21, 2019 - Rapid expansion of interventions could prevent up to 13 million cases of cervical cancer within 50 years
February 21, 2019 - Motif Bio Receives Complete Response Letter From The FDA
February 21, 2019 - Researchers map previously unknown disease in children
February 21, 2019 - A skeptical look at popular diets: Going gluten-free
February 21, 2019 - Podcast: KHN’s ‘What The Health?’ How Safe Are Your Supplements?
February 21, 2019 - Factors associated with increased risk of developing surgical site infections
February 21, 2019 - Anticipatory signals in eye movements can help measure attentive capacity, learning with greater precision
February 21, 2019 - Study explores daily exposure to indoor air pollutants
February 21, 2019 - Evening exercise does not negatively affect sleep, may also reduce hunger
February 21, 2019 - Artificial intelligence technique can be used to identify alcohol misuse in trauma setting
How Does Amyloid Formation Impact Neurodegenerative Disease?

How Does Amyloid Formation Impact Neurodegenerative Disease?

image_pdfDownload PDFimage_print

What is Amyloid Formation?

An amyloid is a fibrous material made from protein.

A protein is a chain of amino acids and, unlike other polymers, the way this chain is arranged in 3D is often unique. The building blocks of protein structures, which are often referred to as a protein’s secondary structure, are mostly alpha-helical, where this chain of amino acids forms helices, or beta-sheets, where these chains form extended strands that stack to form sheet-like structures. In an amyloid, the protein chains form almost exclusively beta-sheets and they stack to form immensely long fibrillar structures.

How is Amyloid Formation Significant?

Amyloids are extremely strong structures, the properties of some of these materials rival steel in terms of their tensile strength (e.g. spider silk) and form the basis of some of the toughest natural glues, such as those allowing sea molluscs to stick to rocks. When these structures form in an uncontrolled way in the wrong biological compartment, they can lead to pathology.

How Was it Linked to Degenerative Diseases?

In degenerative disease and, in particular, in neurodegenerative conditions, the formation of amyloids in the brain seems to entail stable soluble intermediate structures that are toxic to our neurons. One of the first people to link the observation of amyloid plaques and tangles with a neurodegenerative condition was Alois Alzheimer in 1901. Since then, advances in protein science, genetics and cell biology have allowed us to dig deeper and understand where these come from and how they may lead to neuronal cell death.

Why is the Research into Amyloid Formation Particularly Challenging?

Amyloids emerge from natural proteins that are either structure-less or lose their original structures before assembling into an amyloid structure. Each amyloid fibril is made from thousands of highly dynamic protein chains that have so many possible orientations and populate so many different intermediately sized forms that standard structural biology techniques struggle to pin these down. As these intermediate structures are key to the toxic nature of this substance, we need to understand more about these. The literature refers to these molecular species as “oligomers”.

What are You Hoping to Find from Your Research?

In our work, we use pure samples of amyloid beta peptide, a protein that is causative in Alzheimer’s disease and observed how its spontaneous assembly into amyloid in the test tube. We have tested the impact of many different experimental set-ups and found conditions where the assembly occurs in a reliable and consistent manner. This has allowed us to begin to evaluate the ability of different drugs and biological molecules to prevent amyloid formation and even break it down. We can measure the amount of amyloid forming as a function of time but until recently, we have lacked a sensitive way to measure the “oligomers” and characterise their diversity.

How Does Field Flow Fractionation Help You Achieve this?

Asymmetric flow field flow fractionation, or AF4, provides a fantastic method for characterising the different species that arise during the assembly and indeed disassembly of amyloids. Standard fractionation methods that are generally applied to biological molecules are often too limited by the range of molecular weights they can contend with (amyloids are microns long) and by the use of solid surfaces that amyloids tend to stick to. AF4 is a liquid based fractionation method that can separate particles over a huge range, from the very small (sub – nanometres or < 10-9 m) to the very large (microns or 10-6 m). In the same run, we are able to quantify the amounts of different species over this whole range and estimate their molecular properties. When combined with visual techniques like electron or atomic force microscopy, this ability to quantify the material is a huge advance.

How has the AF2000 Helped You Achieve Better Results?

So far, we have used the technology to provide some very much needed quality control in our samples and ensure reliability of our experimental set-up. The sensitivity of amyloid forming material to the environment is notorious and the AF4 has allowed us to establish clear protocols to ensure reproducibility and a stronger interpretation of the data. This will form the first of our publications on this material. We have also begun to measure the formation of oligomers in different conditions and will observe the impact of proposed therapeutic drugs such as G3P protein on amyloids. This is within the framework of our BBSRC (research council) funded grant.

Where Do You See Your Research Going Within Degenerative Diseases?

We will be able to correlate the population of specific oligomers with observables such as toxicity to neurons, and more specifically binding to specific cellular receptors or impact on neuronal cell membranes. The ability of different drugs to impact on these processes will then be able to be characterised.

Where can Our Readers Find Out More About Your Research and the AF2000?

More information can be found on the following webpage:


About Dr Rosie Staniforth

Dr Rosie Staniforth trained as a protein chemist in the field of protein folding and developed one of the first mechanistic descriptions of the GroEL chaperone activity. In 1998, she came to the University of Sheffield (UoS) to train in structural biology and, in particular NMR spectroscopy, working on protein misfolding. Here, she was awarded a Wellcome Trust Career development fellowship and a Royal Society University Research Fellowship, the latter to address the mechanisms of formation of amyloid aggregates.

The model systems on which she has focussed primarily are cystatins, a family of cysteine protease inhibitors including members that cause a hereditary form of cerebral amyloid angiopathy (CAA). In CAA, cystatin C amyloid deposits in brain arteries leading to recurrent stroke and early death. Cystatins also play a role in the sporadic disease, which affects >50% of individuals in their 80s, including 90% of patients with Alzheimer’s disease (AD).

Cystatin C is listed as a strong candidate for a susceptibility gene for late-onset AD. Current work in her group focuses on the molecular details of this role and how it interacts with amyloid β peptide in both CAA and AD. This expertise is now being widened to understanding how natural compounds, both proteins and small molecules, bind to and regulate amyloidogenic proteins at different stages of assembly. Dr Staniforth is currently principal investigator on a BBSRC grant which investigates the molecular basis for the amyloid re-modelling activity of the protein G3P.



Tagged with:

About author

Related Articles