Ubiquitination and SUMOylation of Amyloid and Amyloid-like Proteins in Health and Disease

Abstract

Post-translational modifications (PTMs) play important roles in altering the structure and function of proteins. In this article, we focus on ubiquitination and SUMOylation of amyloidogenic proteins. We discuss the functional contributions of PTMs on proteins involved in amyloid-related diseases as well as the aberrant PTM signatures of the disease agents. In addition, we extend our discussion to the nascent field of functional amyloids, a subclass of amyloids that perform physiological functions. Here, we present examples from mammals and yeast to gain insight into physiological regulation of amyloid-like proteins.

Role of Polyphenols on Gut Microbiota and the Ubiquitin-Proteasome System in Neurodegenerative Diseases

“…A feature of these diseases is genetic mutations which occur in the PrP gene. 135 PrP masses become ubiquitinated similarly to most other protein aqueous inclusions. 148 Moreover, there is a relationship between high levels of ubiquitin-conjugated protein and reduced proteasomal activation.…”

“…Interestingly, astrogliosis is still expressed, and the animals are functionally ruined just similar to APPswe/PS1 age-matched controls . Tau is another amyloid found in AD and is a precursor to neurofibrillary tangles . Morishima-Kawashima et al and Cripps et al identified Tau ubiquitination by mass spectrometry of paired helical filaments, which were separated from AD brain. , Additionally, Morris et al isolated them from mouse brain tissue .…”

“…Generally, Tau can be degraded in two ways: the ubiquitin-dependent proteasome system which results in downstream proteasome destruction of Tau as well as the ubiquitin-independent proteasome system . However, the overexpression of Tau in HEK293T cells (i.e., a highly transfectable derivative of human embryonic kidney 293 cells2) leads to a decrease in the ubiquitination of Tau, which occurs simultaneously with an increase in Tau aggregation and a decrease in Tau destruction. , Notably, there is an important link between acetylation and ubiquitination of Tau, which has recently been investigated. Morris et al understood from mass spectrometry that ubiquitination sites compete with each other for acetylation …”

“…However, E3 ubiquitin ligase parkin is another component which links ubiquitination to pathology. Parkin is produced by the PARK2 gene whose mutation is a well-known genetic cause of PD, and therefore, the mutation of this gene proves the vital function of the ubiquitination in PD . Early onset PD pathology, on the other hand, does not have -syn-rich Lewy body deposits.. Alternatively, a disturbance in parkin function is associated with inhibited mitochondrial function and increased development of tumors …”

“…A feature of these diseases is genetic mutations which occur in the PrP gene . PrP masses become ubiquitinated similarly to most other protein aqueous inclusions .…”