scholarly journals A Concise Review of Amyloidosis in Animals

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Moges Woldemeskel
Keyword(s):  
Microscopic Examination ◽  
Protein Misfolding ◽  
Polarized Light ◽  
Amyloid Deposit ◽  
Clinical Findings ◽  
Wild Animals ◽  
Concise Review ◽  
Underlying Causes ◽  
Congo Red Staining ◽  
Misfolding Diseases

Amyloidosis refers to a group of protein misfolding diseases characterized by deposition of a particular amyloid protein in various organs and tissues of animals and humans. Various types and clinical forms of amyloidosis, in which the pathology and pathogenesis is diverse depending upon the underlying causes and species affected, are reported in domestic and wild animals. The clinical findings are also quite variable consequent to the variation of the tissues and organs involved and the extent of functional disruption of the affected organs in various animal species. The affected organs may be enlarged and exhibit variable pallor grossly, or the amyloid deposit may be discernible only after microscopic examination of the affected tissues. Amyloid appears as a pale eosinophilic homogenous extracellular deposit in tissues. However, microscopic examination and Congo red staining with green birefringence under polarized light are needed to confirm amyloid and differentiate it from other apparently similar extracellular deposits such as collagen and fibrin. Identifying the type of amyloid deposit needs immunohistochemical staining, ultrastructural characterization of the amyloid fibril, and if feasible also genetic studies of the involved species for clinical and prognostic purposes. This paper provides a concise review of the occurrence of amyloidosis in domestic and wild animals.

An Ancillary Tool for the Diagnosis of Amyloid A Amyloidosis in a Variety of Domestic and Wild Animals

2005 ◽  
Vol 42 (2) ◽  
pp. 132-139 ◽  
Author(s):  
S. Shtrasburg ◽  
R. Gal ◽  
E. Gruys ◽  
S. Perl ◽  
B. M. Martin ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Polyacrylamide Gel Electrophoresis ◽  
Amyloid Deposit ◽  
Wild Animals ◽  
Aa Amyloidosis ◽  
Tissue Samples ◽  
Amyloid A ◽  
Congo Red Staining ◽  
Species Specific

Immunohistochemistry, the standard method for diagnosing amyloid A (AA) amyloidosis, is limited in animals because it requires a large array of animal-specific anti-AA antibodies, not commercially available. The Shtrasburg method (SH method) is a highly specific and sensitive technique, helping in the diagnosis and determination of AA amyloidosis in humans. The aim of this study is to determine whether the SH method is applicable in the diagnosis of AA amyloidosis in a variety of animals. Tissue samples were obtained from animals suffering from spontaneous or experimentally induced AA amyloidosis (mice, hamsters, guinea pigs, cheetahs, cats, cows, ducks, a dog, a goose, a chicken, and a turaco). Detection of the amyloid and quantitative evaluation were performed using Congo red staining, and specific AA typing was performed by the potassium permanganate technique. The studied tissues were subjected to the SH method, which confirmed the AA nature of the amyloid deposit, by displaying in polyacrylamide gel electrophoresis protein bands consistent with the molecular weight of the species-specific AA, in all the animals examined, except mice, hamsters, and guinea pigs. N-terminal analysis of these bands corroborated their AA origin. We conclude that the SH method may be used as an ancillary simple tool for the diagnosis of AA amyloidosis in a large number of domestic and wild animals. Moreover, our findings further increase the feasibility of applying this method in humans.

scholarly journals Infrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Francesco Simone Ruggeri ◽  
Johnny Habchi ◽  
Sean Chia ◽  
Robert I. Horne ◽  
Michele Vendruscolo ◽  
...  
Keyword(s):  
Small Molecules ◽  
Single Molecule ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Chemical Sensitivity ◽  
Incomplete Knowledge ◽  
Parkinson’S Diseases ◽  
Aggregation Inhibitor ◽  
Misfolding Diseases

AbstractSignificant efforts have been devoted in the last twenty years to developing compounds that can interfere with the aggregation pathways of proteins related to misfolding disorders, including Alzheimer’s and Parkinson’s diseases. However, no disease-modifying drug has become available for clinical use to date for these conditions. One of the main reasons for this failure is the incomplete knowledge of the molecular mechanisms underlying the process by which small molecules interact with protein aggregates and interfere with their aggregation pathways. Here, we leverage the single molecule morphological and chemical sensitivity of infrared nanospectroscopy to provide the first direct measurement of the structure and interaction between single Aβ42 oligomeric and fibrillar species and an aggregation inhibitor, bexarotene, which is able to prevent Aβ42 aggregation in vitro and reverses its neurotoxicity in cell and animal models of Alzheimer’s disease. Our results demonstrate that the carboxyl group of this compound interacts with Aβ42 aggregates through a single hydrogen bond. These results establish infrared nanospectroscopy as a powerful tool in structure-based drug discovery for protein misfolding diseases.

scholarly journals SAR by kinetics for drug discovery in protein misfolding diseases

2018 ◽  
Vol 115 (41) ◽  
pp. 10245-10250 ◽  
Author(s):  
Sean Chia ◽  
Johnny Habchi ◽  
Thomas C. T. Michaels ◽  
Samuel I. A. Cohen ◽  
Sara Linse ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Protein Misfolding ◽  
Amyloid Beta Peptide ◽  
Oligomer Formation ◽  
Chemical Derivatives ◽  
Structure Activity ◽  
Beta Peptide ◽  
Misfolding Diseases ◽  
Aβ Oligomer

To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure−activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive chemical rules in the case of the amyloid beta peptide (Aβ), which we then exploit to optimize starting compounds to curtail Aβ oligomer formation. We demonstrate this approach by converting an inactive rhodanine compound into an effective inhibitor of Aβ oligomer formation by generating chemical derivatives in a systematic manner. These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers.

Interaction between amyloidogenic proteins and biomembranes in protein misfolding diseases: Mechanisms, contributors, and therapy

2018 ◽  
Vol 1860 (9) ◽  
pp. 1876-1888 ◽  
Author(s):  
Biao Cheng ◽  
Yang Li ◽  
Liang Ma ◽  
Zhuoyi Wang ◽  
Robert B. Petersen ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Amyloidogenic Proteins ◽  
Misfolding Diseases

Noninvasive Detection of Misfolded Proteins in the Brain Using [11C]BF-227 PET

2013 ◽  
pp. 438-445
Author(s):  
Nobuyuki Okamura ◽  
Shozo Furumoto ◽  
Manabu Tashiro ◽  
Katsutoshi Furukawa ◽  
Hiroyuki Arai ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Protein A ◽  
Lewy Bodies ◽  
Protein Aggregates ◽  
Brain Regions ◽  
Postmortem Brain ◽  
In Vivo Detection ◽  
Misfolding Diseases ◽  
The Brain

Alzheimer’s disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched ß-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to ß-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to a-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for ß-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.

scholarly journals Histochemical Differential Diagnosis and Polarization Optical Analysis of Amyloid and Amyloidosis

2006 ◽  
Vol 6 ◽  
pp. 154-168 ◽  
Author(s):  
M. Bély
Keyword(s):  
Differential Diagnosis ◽  
Congo Red ◽  
Early Recognition ◽  
Polarized Light ◽  
Optical Analysis ◽  
Early Start ◽  
Amyloid Deposits ◽  
Protein Fibrils ◽  
Congo Red Staining ◽  
Sensitive Method

Amyloidosis is characterized by extracellular deposition of protein fibrils of chemically heterogeneous composition. Early recognition and identification of amyloid deposits allows an early start of therapy, which may entail a better prognosis. Congo red staining according to Romhányi (1971) is a highly specific and sensitive method for early microscopic recognition of amyloidosis. The main and most important types of amyloidosis may be distinguished by classic histochemical methods of performate pretreatment according to Romhányi (1979), or by KMnO4oxidation according to Wright (1977) followed by Congo red staining and viewed under polarized light. Differences in the speed of breakdown (disintegration) of amyloid deposits according to Bély and Apáthy allow a more precise distinction of various types of amyloid.

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