Table 1.
Summary and references for the major findings described in the review.
| Significant feature | Key findings | References |
|---|---|---|
| Aβ Aggregates in Heart and Brain | Plaque-like amyloid deposits in patients diagnosed with idiopathic dilated cardiomyopathy (iDCM) | Gianni et al., 2010; Troncone et al., 2016; Tublin et al., 2019 |
| Ca2+ Hypothesis | Reduced proteasome activity leads to Ca2+ dysregulation which favors protein misfolding | Uddin et al., 2020 |
| Intracellular Ca2+ homeostasis disruption promotes cell dysfunction and death | Demuro et al., 2005, 2010; Gianni et al., 2010; Yamasaki-Mann et al., 2010; Torres et al., 2011; Demuro and Parker, 2013 | |
| ER Stress in Heart and Brain | ER stress increases in failing hearts | Okada et al., 2004; Guan et al., 2011; Park et al., 2012; Castillero et al., 2015; Uddin et al., 2018, 2020 |
| Inhibition of ER stress due to Aβ overload inhibits neurol apoptosis in AD mice | He et al., 2020 | |
| Physical exercise alleviates cognitive impairment in AD mouse by reducing the expression of abnormal ER stress markers | Hong et al., 2020 | |
| Enhancing UPRER and UPRmt to treat neurodegenerative and cardiovascular disease | ATF6 reprograms proteostasis, induces MANF, a protein folding chaperone in the heart, and downregulates the levels of β-site APP cleaving enzyme in AD models. | Blackwood et al., 2019a; Arrieta et al., 2020; Du et al., 2020 |
| GRP78, an ER Ca2+ dependent chaperone, protects against ischemic myocardial injury and restore ER stress in AD models | Vitadello et al., 2003; Pan et al., 2004; Shintani-Ishida et al., 2006 | |
| Overexpression of LonP1, one of the main mitochondrial proteases, can mitigate cardiac injury during ischemic-reperfusion | Venkatesh et al., 2019 | |
| Enhancement of UPRmt in pressure-overloaded mice hearts significantly improves cardiomyocyte survival and and cardiac contractile function | Smyrnias et al., 2019 | |
| Targeting UPS to treat neurodegenerative and cardiovascular disease | LMP-2, a proteasome subunit, allows the breakdown of pre-existing sarcomeres, required for cardiac remodeling processes. | Petersen et al., 2020 |
| Triad3A, a E3 ligase, attenuates cardiac hypertrophy | Lu et al., 2020 | |
| Resveratrol (RES) blocks immunoproteasome subunits (β1i, β2i and β5i) and reduces cardiac hypertrophy | Chen et al., 2019; Xie et al., 2020; Yan et al., 2020 | |
| cAMP/PKA enhances clearance of aggregation-prone proteins in neurodegenerative diseases | Lin et al., 2013; Ranek et al., 2013; Lokireddy et al., 2015; Myeku et al., 2016 | |
| cGMP/PKG positively regulates proteasome-mediated proteolysis degrading mutated CryAB in desmin cardiomyopathy | Liu et al., 2006a,b; Ranek et al., 2013 | |
| Enhancing autophagy to treat neurodegenerative and cardiovascular disease | TRAF6/p62 expression may relieve Aβ-mediated inhibition of p75 NTR polyubiquitination and restore neuronal cell survival | Babu et al., 2005; Geetha et al., 2012; Chen et al., 2020 |