Minimotifs dysfunction is pervasive in neurodegenerative disorders

Alzheimers Dement (N Y). 2018 Jul 25:4:414-432. doi: 10.1016/j.trci.2018.06.005. eCollection 2018.


Minimotifs are modular contiguous peptide sequences in proteins that are important for posttranslational modifications, binding to other molecules, and trafficking to specific subcellular compartments. Some molecular functions of proteins in cellular pathways can be predicted from minimotif consensus sequences identified through experimentation. While a role for minimotifs in regulating signal transduction and gene regulation during disease pathogenesis (such as infectious diseases and cancer) is established, the therapeutic use of minimotif mimetic drugs is limited. In this review, we discuss a general theme identifying a pervasive role of minimotifs in the pathomechanism of neurodegenerative diseases. Beyond their longstanding history in the genetics of familial neurodegeneration, minimotifs are also major players in neurotoxic protein aggregation, aberrant protein trafficking, and epigenetic regulation. Generalizing the importance of minimotifs in neurodegenerative diseases offers a new perspective for the future study of neurodegenerative mechanisms and the investigation of new therapeutics.

Keywords: Aggregate; Binding; Epigenetics; GWAS; Genetics; Histone code; Minimotif; Posttranslational modification; Trafficking.