Amyloids – A form of Cytoplasmic fibrils in humans

My next interest was to investigate in which form the Cytoplasmic fibrils can occur in humans.

One of my presumptions is that Morgellons Disease is not only  transmitted over insects which is the main suspect,  but that is also takes pre-dominant ailments that leads to a notable, visual outbreak and signs of typical symptoms.

I also suspect that a dysfunctional endocrine system or other pre-existent malfunctions are also involved.

We have studied that the Herpes Virus for example, many Morgellons Sufferers reported to be infected with, is one factor also a type of diabetes and thyroid dysfunctions.

Further research has revealed that many diseases histological examined show significant structural properties of Cytoplasmic fibrils or Amyloids and confirms my theory.

Listed below you can see which diseases show typical signs of Amyloids.

But first, here a link to explain the term ‘Amyloid and a few excerpts I found related to my other subjects.

http://en.wikipedia.org/wiki/Peptide

http://en.wikipedia.org/wiki/Amyloid

We remember that the p10 protein is capable of forming polymer filaments. Polymer proteins are also called Polypeptides.

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various other neurodegenerative diseases.

A more recent, biophysical definition is broader, including any polypeptide which polymerizes to form a cross-beta structure, in vivo, or in vitro.

Amyloid polymerization (aggregation or non-covalent polymerization) is generally sequence-sensitive, that is, causing mutations in the sequence can prevent self-assembly, especially if the mutation is a beta-sheet breaker, such as proline. For example, humans produce amylin, an amyloidogenic peptide associated with type II diabetes.

The reasons for amyloid association with disease is unclear. In some cases, the deposits physically disrupt tissue architecture, suggesting disruption of function by some bulk process. An emerging consensus implicates prefibrillar intermediates, rather than mature amyloid fibers, in causing cell death.

see also: http://en.wikipedia.org/wiki/Apoptosis

Some diseases featuring Amyloids:

  • Diabetes melitus Type II
  • Alzheimer Disease
  • Mad Cow’s Disease
  • Rheumatoid Arthritis
  • Familial amyloid polyneuropathy
  • Thyroid Carcinoma
  • Inclusion Body Myositis

Here is an image of Amyloid assembly mechanisms:

Amyloid2

 

Amyloid aggregation mechanisms

The study of amyloid structure and growth has been motivated by their implication in many human diseases.

There are ~20 diseases associated with excessive deposits of amyloid plaques in the affected tissue or organ including Alzheimer?s disease (AD), Parkinson?s disease (PD), type II diabetes, and spongiform encephalopathies.

In these disease states, proteins that are normally soluble undergo aggregation to form various intermediates and amyloidogenic species.

These species subsequently assemble to generate insoluble fibrils that accumulate in the affected tissues or organs.

A detailed understanding of amyloid growth mechanisms will allow new approaches to the prevention of amyloid formation and better diagnostics for early detection of amyloidogenic diseases.

A molecular-level mechanism of amyloid growth must include details as to when the protein misfold occurs and how it is influenced by the dynamics of protein structure.

To determine the physical interactions and structural changes involved in the amyloid assembly mechanism, we study effect of environmental variables such as temperature, pH, helix promoting solvents, denaturants, and reducing agents.

The environmental effect on aggregation is expected to be species-dependent reflecting a possible hierarchy of structural interactions.

During their life cycle proteins undergo many types of conformational changes.  The first type of conformational change is the process of protein folding. 

The polypeptide must fold into its active three-dimensional structure before it is degraded by cellular proteases or aggregates.

Aggregation of soluble polypeptides or proteins into insoluble amyloid fibrils with cross-ß structural motif has been observed in the progression of a great variety of diseases.

Experiments suggest that amyloid fibrils share a common core filament structure, irrespective of the nature of their precursor proteins.

source: http://talaga.rutgers.edu/research/amyloid.php

Overview of amyloid assembly mechanisms

Amyloid – any fibril, plaque, seed, or aggregate that has the characteristic cross-ß sheet structure.
Amyloidogenic precursor – a protein or peptide that upon incubation under appropriate conditions will form amyloid fibrils or plaques.
Amyloid fibril – long ribbons of amyloid ~10nm in diameter and >100nm in length. Most often observed in vitro.
Amyloid plaque – the form of amyloid most often found in vivo – often comprised of aggregated amyloid fibrils.
Amyloid protofibril/filament – a species of amyloid smaller in diameter (3-6nm) and length(<100nm) than typical for amyloid fibrils, thought to be a possible direct precursor to amyloid fibrils perhaps through lateral aggregation.
Amyloid seed (or template) – a species of a critical size or structure that rapidly elongates to form larger amyloid species possibly by providing a proper scaffold for amyloid assembly
Amyloidogenic oligomer – A small aggregate of precursor that is smaller than the critical “seed” size but still may have some of the structural characteristics of amyloid.
Amyloidogenic fold – a structure of the precursor that must be accessed prior to amyloidogenic aggregation, thought to retain substantial secondary structure possibly including some of the native fold. It could be related to a misfolded or molten globule structure.
Folded state – The native (functional) state of the precursor.
Folding intermediate – A partially folded or misfolded structure of the precursor. These partially folded structures are potentially the same as or precursors to amyloidogenic folds.
Denatured state – The unfolded state of the precursor.
Unstructured aggregate – Completely or partially denatured proteins tend to aggregate non-specifically without forming a particular structural motif.

source: http://talaga.rutgers.edu/research/amyloid.php

~ by k&k on September 7, 2009.

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