Neurodegeneration & imperfect ageing: Technological limitations and challenges?

Cellular homeostasis is regulated by the protein quality control (PQC) machinery, comprising multiple chaperones and enzymes. Studies suggest that the loss of the PQC mechanisms in neurons may lead to the formation of abnormal inclusions that may lead to neurological disorders and defective aging. The questions could be raised how protein aggregate formation precisely engenders multifactorial molecular pathomechanism in neuronal cells and affects different brain regions? Such questions await thorough investigation that may help us understand how aberrant proteinaceous bodies lead to neurodegeneration and imperfect aging. However, these studies face multiple technological challenges in utilizing available tools for detailed characterizations of the protein aggregates or amyloids and developing new techniques to understand the biology and pathology of proteopathies. The lack of detection and analysis methods has decelerated the pace of the research in amyloid biology. Here, we address the significance of aggregation and inclusion formation, followed by exploring the evolutionary contribution of these structures. We also provide a detailed overview of current state-of-the-art techniques and advances in studying amyloids in the diseased brain. A comprehensive understanding of the structural, pathological, and clinical characteristics of different types of aggregates (inclusions, fibrils, plaques, etc.) will aid in developing future therapies.