Amyloid Proteins and Peripheral Neuropathy

Abstract

Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature—deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for “peripheral amyloid neuropathies”.

The coral crunch: Amyloidoma

“…Commonly incriminated sites are lower extremities, cutaneous surfaces or subcutaneous tissue. The condition is idiopathic or may arise as a consequence of multiple myeloma, plasmacytoid lymphoma and in individuals with chronic in lammation or on long-term dialysis [5,6].…”

“…c) Competent immuno-histochemical analysis and con irmation with sophisticated techniques is necessitated [5,6].…”

“…Localized amyloidosis appears within the head and neck region and is predominantly discerned in larynx or trachea whereas amyloidoma or diffuse enlargement of the tongue is exceptional. A polypoid tumefaction of variable magnitude protruding into superimposed cutaneous or mucosal surface can be exhibited [6,7].…”

“…Insulin-derived amyloidosis exhibits a solitary (90%), irm or soft subcutaneous nodule of variable magnitude appearing at the site of insulin injections [6,7]. https://doi.org/10.29328/journal.adr.1001013…”

Novel Insights into Molecular Mechanisms of Chronic Pain

“…As potential mechanisms, the authors discuss protein–membrane interactions, ER stress, mitochondrial dysfunction and inflammatory mechanisms in particular with contribution of macrophages and microglia, and disturbances in autophagic processes as well as microangiopathy. With regard to the collected data, the authors suggest that amyloid disturbances might be involved in neuropathy in some common diseases which have not yet been considered as amyloid neuropathies and that further research in this field is very important [ 19 ].…”