Realization of Amyloid-like Aggregation as a Common Cause for Pathogenesis in Diseases

Abstract

Amyloids were conventionally referred to as extracellular and intracellular accumulation of Aβ42 peptide, which causes the formation of plaques and neurofibrillary tangles inside the brain leading to the pathogenesis in Alzheimer’s disease. Subsequently, amyloid-like deposition was found in the etiology of prion diseases, Parkinson’s disease, type II diabetes, and cancer, which was attributed to the aggregation of prion protein, α-Synuclein, islet amyloid polypeptide protein, and p53 protein, respectively. Hence, traditionally amyloids were considered aggregates formed exclusively by proteins or peptides. However, since the last decade, it has been discovered that other metabolites, like single amino acids, nucleobases, lipids, glucose derivatives, etc., have a propensity to form amyloid-like toxic assemblies. Several studies suggest direct implications of these metabolite assemblies in the patho-physiology of various inborn errors of metabolisms like phenylketonuria, tyrosinemia, cystinuria, and Gaucher’s disease, to name a few. In this review, we present a comprehensive literature overview that suggests amyloid-like structure formation as a common phenomenon for disease progression and pathogenesis in multiple syndromes. The review is devoted to providing readers with a broad knowledge of the structure, mode of formation, propagation, and transmission of different extracellular amyloids and their implications in the pathogenesis of diseases. We strongly believe a review on this topic is urgently required to create awareness about the understanding of the fundamental molecular mechanism behind the origin of diseases from an amyloid perspective and possibly look for a common therapeutic strategy for the treatment of these maladies by designing generic amyloid inhibitors.

Association between Parkinson’s Disease and Cancer: New Findings and Possible Mediators

“…Naskar and Goar analyzed published data and proposed a generic amyloid hypothesis considering that amyloidogenic proteins may be responsible for the etiology of a plethora of diseases including PD and cancer [61]. The hypothesis assumes that traditional amyloids are formed not only by proteins or peptides but also by metabolites, including single amino acids, nucleobases, lipids, and glucose derivatives.…”

Translating Biospectroscopy Techniques to Clinical Settings: A New Paradigm in Point-of-Care Screening and/or Diagnostics

“…Although much work applying and investigating the usefulness of biospectroscopy has been undertaken in the oncology field, the methodology has also been successfully studied in many other areas, including cardiology [41], infectious diseases [42,43], amyloid pathologies [44], fibromyalgia syndrome [45], and mood disorders [46]. There is now a comprehensive body of literature containing multiple studies investigating and validating different aspects of this approach.…”

Scaffold Morphing and In Silico Design of Potential BACE-1 (β-Secretase) Inhibitors: A Hope for a Newer Dawn in Anti-Alzheimer Therapeutics

“…It results due to neuron degeneration in the cortical and hippocampal regions of the brain, which control learning, memory, and cognitive abilities [ 3 ]. Alzheimer’s disease (AD) is associated with the formation of senile plaques and neurofibrillary tangles in the brain, which causes dementia and memory loss [ 4 , 5 , 6 ]. The primary hallmark of Alzheimer’s disease is the accumulation of β-amyloid proteins in the synapses of the cortical neurons and the formation of tau tangles inside the neurons due to the twisting of tau protein fibers.…”