The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).

Defects in axonal transport are often associated with a wide variety of neurological diseases including Alzheimer's disease (AD).␤-Amyloid (A␤) is a major component of neuritic plaques associated with pathological conditions of AD brains. Here, we report that a brief exposure of cultured hippocampal neurons to A␤ molecules resulted in rapid and severe impairment of mitochondrial transport without inducing apparent cell death and significant morphological changes. Such acute inhibition of mitochondrial transport was not associated with a disruption of mitochondria potential nor involved aberrant cytoskeletal changes. A␤ also did not elicit significant Ca 2ϩ signaling to affect mitochondrial trafficking. However, stimulation of protein kinase A (PKA) by forskolin, cAMP analogs, or neuropeptides effectively alleviated the impairment. We also show that A␤ inhibited mitochondrial transport by acting through glycogen synthase kinase 3␤ (GSK3␤). Given that mitochondria are crucial organelles for many cellular functions and survival, our findings thus identify an important acute action of A␤ molecules on nerve cells that could potentially contribute to various abnormalities of neuronal functions under AD conditions. Manipulation of GSK3␤ and PKA activities may represent a key approach for preventing and alleviating A␤ cytotoxicity and AD pathological conditions.

Negative bHLH transcription factor Hes1 can inhibit neural stem cells (NSCs) from precocious neurogenesis through repressing proneural gene expression; therefore, sustenance of Hes1 expression is crucial for NSC pool maintenance. Here we find that Ids, the dominant-negative regulators of proneural proteins, are expressed prior to proneural genes and share an overlapping expression pattern with Hes1 in the early neural tube of chick embryos. Overexpression of Id2 in the chick hindbrain upregulates Hes1 expression and inhibits proneural gene expression and neuronal differentiation. By contrast, Hes1 expression decreases, proneural gene expression expands, and neurogenesis occurs precociously in Id1;Id3 double knockout mice and in Id1-3 RNAi-electroporated chick embryos. Mechanistic studies show that Id proteins interact directly with Hes1 and release the negative feedback autoregulation of Hes1 without interfering with its ability to affect other target genes. These results indicate that Id proteins participate in NSC maintenance through sustaining Hes1 expression in early embryos.