Protein aggregation, misfolding and consequential human neurodegenerative diseases

Abstract

Proteins are major components of the biological functions in a cell. Biology demands that a protein must fold into its stable three-dimensional structure to become functional. In an unfavorable cellular environment, protein may get misfolded resulting in its aggregation. These conformational disorders are directly related to the tissue damage resulting in cellular dysfunction giving rise to different diseases. This way, several neurodegenerative diseases such as Alzheimer, Parkinson Huntington diseases and amyotrophic lateral sclerosis are caused. Misfolding of the protein is prevented by innate molecular chaperones of different classes. It is envisaged that work on this line is likely to translate the knowledge into the development of possible strategies for early diagnosis and efficient management of such related human diseases. The present review deals with the human neurodegenerative diseases caused due to the protein misfolding highlighting pathomechanisms and therapeutic intervention.

Exploiting the therapeutic potential of ready-to-use drugs: Repurposing antibiotics against amyloid aggregation in neurodegenerative diseases

“…Over the years, this hypothesis has been modified to implicate soluble prefibrillar intermediates as the neurotoxic species. Nevertheless, the process of protein amyloid aggregation remains the main feature of neurodegenerative diseases until today (Beyreuther and Masters, 1991;Hardy and Allsop, 1991;Hardy and Higgins, 1992;Karran et al, 2011;Sami et al, 2017;Selkoe, 1991Selkoe et al, 2016.…”

Oxidative stress triggers aggregation of GFP-tagged Hsp31p, the budding yeast environmental stress response chaperone, and glyoxalase III

“…In addition to these purposeful assemblies, eukaryotic cells can be cluttered with protein aggregates, which are generally regarded as pathogenic or at least as a burden that reduces cellular fitness. The best-known examples in humans are aggregates that form in the central nervous system and lead to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, Creutzfeldt-Jacob, tauopathies and amyotrophic lateral sclerosis (see recent reviews (Renner and Melki 2014 ; Sami et al 2017 )). The latter disease may result from the inefficient disposal of stress granules (Monahan et al 2016 ).…”

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

“…The lack, on the therapeutic front, of treatments for slowing the rate of occurrence of NDs, these often become devastating, not only for the patients and their families (for care and dependency), but often also leaving a deep scar in terms of the mounting economic burden. With huge socioeconomic constraints, the etiology of NDs [Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and others] has become a burning issue that needs properly addressing, not only in terms of understanding the disease mechanism, but also in terms of the advancement of developing potential treatment regimes that can control the progression of the NDs [2][3][4][5][6][7].…”