The Importance of Protein Post-Translational Modifications in the Pathogenesis and Progression of Neurodegenerative Diseases

Abstract

The chemical modifications of proteins during or after their biosynthesis via the covalent attachment of functional groups or proteolytic cleavage at specific amino acids are termed protein post-translational modifications. A more comprehensive understanding of the molecular mechanisms that trigger pathogenesis or progression of neurodegenerative diseases (NDDs) is a prerequisite to developing new treatment options. Alzheimer’s disease is the most common NDD and accounts for 60–80% of all cases of dementia. Approximately 1% of individuals over the age of 60 years and close to 5% of the population aged 80 or older suffer from Parkinson’s disease, the second most common NDD and most common movement disorder. Amyotrophic lateral sclerosis is a fatal, incurable NDD characterised by the loss of upper and lower motor neurons. Spinocerebellar ataxias are a heterogeneous group of >27 different autosomal dominant NDDs that share the phenotypical core feature of ataxia and are characterised by degenerative and atrophic changes in the central nervous system, primarily affecting the cerebellum.