Cell Biochemistry and Biophysics

, Volume 61, Issue 2, pp 237–250 | Cite as

Defective Protein Folding and Aggregation as the Basis of Neurodegenerative Diseases: The Darker Aspect of Proteins

  • Aabgeena NaeemEmail author
  • Naveed Ahmad Fazili
Review Paper


The ability of a polypeptide to fold into a unique, functional, and three-dimensional structure depends on the intrinsic properties of the amino acid sequence, function of the molecular chaperones, proteins, and enzymes. Every polypeptide has a finite tendency to misfold and this forms the darker side of the protein world. Partially folded and misfolded proteins that escape the cellular quality control mechanism have the high tendency to form inter-molecular hydrogen bonding between the same protein molecules resulting in aggregation. This review summarizes the underlying and universal mechanism of protein folding. It also deals with the factors responsible for protein misfolding and aggregation. This article describes some of the consequences of such behavior particularly in the context of neurodegenerative conformational diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis and other non-neurodegenerative conformational diseases such as cancer and cystic fibrosis etc. This will encourage a more proactive approach to the early diagnosis of conformational diseases and nutritional counseling for patients.

Graphical Abstract


Aggregation Conformational diseases Protein misfolding Molecular chaperones 



The authors are highly thankful for the facilities obtained at AMU Aligarh. Financial support from the Department of Science and Technology, New Delhi in the form of project (SR/LS-0292/2007) and Council of Scientific and Industrial Research in the form of project No. 37(1365)/09/EMR-II is gratefully acknowledged.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia

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