Involvement of molecular chaperone in protein-misfolding brain diseases.

Protein misfolding causes aggregation and build-up in a variety of brain diseases. There are numeral molecules that are linked with the protein homeostasis mechanism. Molecular chaperones are one of such molecules that are responsible for protection against protein misfolded and aggregation-induced neurotoxicity. Many studies have explored the participation of molecular chaperones in Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, and Huntington's diseases. In this review, we highlighted the constructive role of molecular chaperones in neurological diseases characterized by protein misfolding and aggregation and their capability to control aberrant protein interactions at an early stage thus successfully suppressing pathogenic cascades. A comprehensive understanding of the protein misfolding associated with brain diseases and the molecular basis of involvement of chaperone against aggregation-induced cellular stress might lead to the progress of new therapeutic intrusion-related to protein misfolding and aggregation.

Combined Assessment of Functional and Metabolic Performance of Human Donor Hearts: Possible Application in Donation After Circulatory Death.

BACKGROUND: Donation after circulatory death (DCD) represents an increasing source of organs. However, evaluating the suitability of DCD hearts for transplantation represents a challenge. Contractile function is the ultimate determinant of recovery. We developed a novel technique in an ex vivo rig for the measurement of contractility using intraventricular balloons. We compared this technique with the measurement of lactate metabolism, the current gold standard. METHODS: Human DCD (n = 6) and donation after brain death (n = 6) hearts were preserved by perfusion with a cold oxygenated crystalloid solution for 4 h, transferred to a blood perfusion rig at 37 °C where balloons were inserted into the left (LV) and right (RV) ventricles to measure developed pressure (DP = systolic minus diastolic). Perfusate lactate levels were measured for metabolic assessment. Concordance between LVDP and lactate was assessed during 4 h using cutoffs for LVDP of 70 mm Hg and for lactate of 10 mmol/L. RESULTS: Measurements of contractile function (LVDP) and metabolism (lactate levels) were deemed concordant in 7 hearts with either a high LVDP (mean 100 mm Hg) with low lactate (mean 6.7 mmol/L)) or a low LVDP (15 mm Hg) with high lactate (mean 17.3 mmol/). In the remaining 5 hearts, measurements were deemed discordant: 4 hearts had high LVDP (mean 124 mm Hg), despite high lactate levels 17.3 mmol/L) and 1 had low LVDP (54 mm Hg) but low lactate (6.9 mmol/L). CONCLUSIONS: The intraventricular balloon technique provides useful information regarding contractile recovery of donor hearts that if combined with lactate metabolism has potential application for the evaluation of DCD and marginal donation after brain death hearts before transplant.