Contents
14 August 2019
Vol 11, Issue 505
Vol 11, Issue 505
Research Articles
- Disrupted hippocampal growth hormone secretagogue receptor 1α interaction with dopamine receptor D1 plays a role in Alzheimer′s disease
GHSR1α and DRD1 coactivation preserves the integrity of hippocampal synapses in Alzheimer’s disease.
- Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial
An oral small molecule turns on the transcription of human interleukin-12, with biological effects in patients with recurrent high-grade gliomas.
- The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk
Common variants in the microglia-specific MS4A gene cluster modify risk for late-onset Alzheimer’s disease and modulate extracellular soluble TREM2.
- MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21
CDK4/6 inhibition becomes effective in preclinical models of melanoma when combined with MDM2 antagonism.
- Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi
Administering an additional dose of rotavirus vaccine at 9 months of age in Malawi is predicted to lead to only modest improvements in vaccine impact.
Editors' Choice
- Broadening vaccine strategies to induce HIV broadly neutralizing antibodies
Vaccination with anti-idiotype antibodies can activate and target germline B cell precursors of HIV broadly neutralizing antibodies.
- Better living through your gut microbes
Correcting gut microbial dysbiosis improves health and life span in a mouse model of accelerated aging by restoring intestinal bile acid and small-molecule metabolite balance.
- Immune-orthogonal orthologs: The solution for genome editing?
Immune-orthogonal Cas9 allows for genome editing in pre-immunized mice.
About The Cover
ONLINE COVER Feeding Starving Synapses. Loss of hippocampal synapses (pictured) is a prominent pathological change in Alzheimer's disease (AD) and is believed to contribute to memory impairments. Using postmortem hippocampal brain tissue samples from patients with AD and an AD mouse model, Tian and colleagues now decipher a mechanism for hippocampal synapse loss in AD. They show that the pathogenic peptide β-amyloid binds to the receptor for the hunger hormone ghrelin (GHSR1α) and blocks its activity. This inhibition impaired dopamine receptor signaling, causing synaptic loss and memory impairments in mice. Concomitant activation of both the dopamine receptor and GHSR1α rescued synaptic function and improved cognition in AD mice. [CREDIT: KTSDESIGN/GETTY IMAGES]
