Muscle–Brain crosstalk in cognitive impairment

Sarcopenia is an age-related, involuntary loss of skeletal muscle mass and strength. Alzheimer's disease (AD) is the most common cause of dementia in elderly adults. To date, no effective cures for sarcopenia and AD are available. Physical and cognitive impairments are two major causes of disability in the elderly population, which severely decrease their quality of life and increase their economic burden. Clinically, sarcopenia is strongly associated with AD. However, the underlying factors for this association remain unknown. Mechanistic studies on muscle–brain crosstalk during cognitive impairment might shed light on new insights and novel therapeutic approaches for combating cognitive decline and AD. In this review, we summarize the latest studies emphasizing the association between sarcopenia and cognitive impairment. The underlying mechanisms involved in muscle–brain crosstalk and the potential implications of such crosstalk are discussed. Finally, future directions for drug development to improve age-related cognitive impairment and AD-related cognitive dysfunction are also explored

Nanoparticles and nanogel drug compositions for treatment of age-related macular degeneration

Disclosed are nanoparticles and nanogel drug compositions and the use thereof for treating age-related macular degeneration

Deletion of Kvβ2 (AKR6) Attenuates Isoproterenol Induced Cardiac Injury with Links to Solute Carrier Transporter SLC41a3 and Circadian Clock Genes

Kvβ subunits belong to the aldo-keto reductase superfamily, which plays a significant role in ion channel regulation and modulates the physiological responses. However, the role of Kvβ2 in cardiac pathophysiology was not studied, and therefore, in the present study, we hypothesized that Kvβ2 plays a significant role in cardiovascular pathophysiology by modulating the cardiac excitability and gene responses. We utilized an isoproterenol-infused mouse model to investigate the role of Kvβ2 and the cardiac function, biochemical changes, and molecular responses. The deletion of Kvβ2 attenuated the QTc (corrected QT interval) prolongation at the electrocardiographic (ECG) level after a 14-day isoproterenol infusion, whereas the QTc was significantly prolonged in the littermate wildtype group. Monophasic action potentials verified the ECG changes, suggesting that cardiac changes and responses due to isoproterenol infusion are mediated similarly at both the in vivo and ex vivo levels. Moreover, the echocardiographic function showed no further decrease in the ejection fraction in the isoproterenol-stimulated Kvβ2 knockout (KO) group, whereas the wildtype mice showed significantly decreased function. These experiments revealed that Kvβ2 plays a significant role in cardiovascular pathophysiology. Furthermore, the present study revealed SLC41a3, a major solute carrier transporter affected with a significantly decreased expression in KO vs. wildtype hearts. The electrical function showed that the decreased expression of SLC41a3 in Kvβ2 KO hearts led to decreased Mg2+ responses, whereas, in the wildtype hearts, Mg2+ caused action potential duration (APD) shortening. Based on the in vivo, ex vivo, and molecular evaluations, we identified that the deletion of Kvβ2 altered the cardiac pathophysiology mediated by SLC41a3 and altered the NAD (nicotinamide adenine dinucleotide)-dependent gene responses

Nanoparticles and nanogel drug compositions for treatment of age-related macular degeneration

Disclosed are nanoparticles and nanogel drug compositions and the use thereof for treating age-related macular degeneration

MicroRNA-301a mediated regulation of Kv4.2 in diabetes: identification of key modulators.

Diabetes is a metabolic disorder that ultimately results in major pathophysiological complications in the cardiovascular system. Diabetics are predisposed to higher incidences of sudden cardiac deaths (SCD). Several studies have associated diabetes as a major underlying risk for heart diseases and its complications. The diabetic heart undergoes remodeling to cope up with the underlying changes, however ultimately fails. In the present study we investigated the changes associated with a key ion channel and transcriptional factors in a diabetic heart model. In the mouse db/db model, we identified key transcriptional regulators and mediators that play important roles in the regulation of ion channel expression. Voltage-gated potassium channel (Kv4.2) is modulated in diabetes and is down regulated. We hypothesized that Kv4.2 expression is altered by potassium channel interacting protein-2 (KChIP2) which is regulated upstream by NFkB and miR-301a. We utilized qRT-PCR analysis and identified the genes that are affected in diabetes in a regional specific manner in the heart. At protein level we identified and validated differential expression of Kv4.2 and KChIP2 along with NFkB in both ventricles of diabetic hearts. In addition, we identified up-regulation of miR-301a in diabetic ventricles. We utilized loss and gain of function approaches to identify and validate the role of miR-301a in regulating Kv4.2. Based on in vivo and in vitro studies we conclude that miR-301a may be a central regulator for the expression of Kv4.2 in diabetes. This miR-301 mediated regulation of Kv4.2 is independent of NFkB and Irx5 and modulates Kv4.2 by direct binding on Kv4.2 3'untranslated region (3'-UTR). Therefore targeting miR-301a may offer new potential for developing therapeutic approaches