Cognitive Dysfunction in Huntington's Disease: Mechanisms and Therapeutic Strategies Beyond BDNF

One of the main focuses in Huntington's disease (HD) research, as well as in most of the neurodegenerative diseases, is the development of new therapeutic strategies, as currently there is no treatment to delay or prevent the progression of the disease. Neuronal dysfunction and neuronal death in HD are caused by a combination of interrelated pathogenic processes that lead to motor, cognitive and psychiatric symptoms. Understanding how mutant huntingtin impacts on a plethora of cellular functions could help to identify new molecular targets. Although HD has been classically classified as a neurodegenerative disease affecting voluntary movement, lately cognitive dysfunction is receiving increased attention as it is very invalidating for patients. Thus, an ambitious goal in HD research is to find altered molecular mechanisms that contribute to cognitive decline. In this review we have focused on those findings related to corticostriatal and hippocampal cognitive dysfunction in HD, as well as on the underlying molecular mechanisms, which constitute potential therapeutic targets. These include alterations in synaptic plasticity, transcriptional machinery, and neurotrophic and neurotransmitter signaling. This article is protected by copyright. All rights reserved

‘‘What’ ’ and ‘‘Where’ ’ in Word Reading: Ventral Coding of Written Words Revealed by Parietal Atrophy Abstract

& The visual system of literate adults develops a remarkable perceptual expertise for printed words. To delineate the aspects of this competence intrinsic to the occipitotemporal ‘‘what’ ’ pathway, we studied a patient with bilateral lesions of the occipitoparietal ‘‘where’ ’ pathway. Depending on critical geometric features of the display (rotation angle, letter spacing, mirror reversal, etc.), she switched from a good performance, when her intact ventral pathway was sufficient to encode words, to severely impaired reading, when her parietal lesions prevented the use of alternative reading strategies as a result of spatial and attentional impairments. In particular, reading was disrupted (a) by rotating word by more than 508, providing an approximation of the invariance range for words encodin