Genetic zebrafish models of neurodegenerative diseases.
As a consequence of the widespread use of zebrafish in developmental biology studies, an extensive array of experimental tools and techniques has been assembled; it has recently become apparent that these might be exploited in the analysis of human neurodegenerative diseases. A surprising degree of functional conservation has been demonstrated between human genes implicated in neurodegenerative diseases and their zebrafish orthologues. In zebrafish models of recessive parkinsonism, Parkin or Pink1 knockdown gave rise to specific loss of dopamine neurons; in a zebrafish model of recessive spinal muscular atrophy, loss of Smn1 function caused specific motor axonal defects. In addition, pathological features of several dominant diseases were replicated by transgenic over-expression of mutant human proteins, including Tau, Huntingtin, and SOD1. In some cases, conservation of relevant cellular pathways was sufficient that disease-specific posttranslational changes to the respective proteins were found in the zebrafish models. These data collectively suggest that the zebrafish can be an appropriate setting in which to model the molecular events underlying human neuropsychiatric disease. Consequently, novel findings yielded by studies in zebrafish models may be applicable to human diseases; this is an exciting prospect, in view of the many potential uses of zebrafish models, for example, screening for lead therapeutic compounds, rapid functional assessments of putative modifier genes, and live observation of pathogenic mechanisms in vivo.
Bandmann
Oliver
O
Academic Neurology Unit, Department of Neuroscience, University of Sheffield, UK. o.bandmann@sheffield.ac.uk
Burton
Edward A
EA
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish / Q000235:genetics*