The role of the glycerol transporter channel Fps1p in cellular proteostasis during enhanced proteotoxic stress.

In response to osmotic shock, the components of high-osmolarity glycerol (HOG) pathway regulate the level of intracellular glycerol in yeast and ensure cell survival. Glycerol is a compatible solute and a stabiliser of proteins. Its role in maintaining proteostasis is less explored.

Stabilization of elongated polyglutamine tracts by a helical peptide derived from N-terminal huntingtin.

In Huntington's disease, the length of the polyglutamine tract in the mutant protein correlates positively with the formation of aggregates and disease symptoms and severity of the disease. Some disease-modifying factors exist. However, no organized study has been carried out to investigate the effect of polyglutamine length in the mutant protein on the efficacy of a therapeutic strategy.

Discrete roles of trehalose and Hsp104 in inhibition of protein aggregation in yeast cells.

Heat shock response (HSR) is an important element of cellular homeostasis. In yeast, HSR comprises of the heat shock proteins (Hsps) and the osmolytes trehalose and glycerol. The respective roles of trehalose and Hsp104 in regulating protein aggregation remain ambiguous.

Does N-terminal huntingtin function as a 'holdase' for inhibiting cellular protein aggregation?

Proteolytic cleavage of huntingtin gives rise to N-terminal fragments. While the role of truncated mutant huntingtin is described in Huntington's disease (HD) pathogenesis, the function of N-terminal wild-type protein is less studied. The yeast model of HD is generated by the presence of FLAG tag and absence of polyproline tract as flanking sequences of the elongated polyglutamine stretch.

Nicotine slows down oligomerisation of α-synuclein and ameliorates cytotoxicity in a yeast model of Parkinson's disease.

Several retrospective epidemiological reports have indicated an inverse correlation between smoking and development of Parkinson's disease (PD). This has mostly been attributed to the neuroprotective role of nicotine in stimulating nicotinic acetylcholine receptors and dopaminergic neurons which are damaged in PD. One of the characteristic features of PD is the intraneuronal deposition of globular inclusions of the intrinsically disordered protein α-synuclein as Lewy bodies.

Challenges with osmolytes as inhibitors of protein aggregation: Can nucleic acid aptamers provide an answer?

Protein aggregation follows some common motifs. Whether in the formation of inclusion bodies in heterologous overexpression systems or inclusions in protein conformational diseases, or aggregation during storage or transport of protein formulations, aggregates form cross beta-sheet structures and stain with amyloidophilic dyes like Thioflavin T and Congo Red, irrespective of the concerned protein. Traditionally, osmolytes are used to stabilize proteins against stress conditions.

Cellular toxicity of yeast prion protein Rnq1 can be modulated by N-terminal wild type huntingtin.

Aggregation of the N-terminal human mutant huntingtin and the consequent toxicity in the yeast model of Huntington's disease (HD) requires the presence of Rnq1 protein (Rnq1p) in its prion conformation [RNQ1(+)]. The understanding of interaction of wild-type huntingtin (wt-Htt) with the amyloidogenic prion has some gaps. In this work, we show that N-terminal fragment of wt-Htt (N-wt-Htt) ameliorated the toxic effect of [RNQ1(+)] depending on expression levels of both proteins.