Animal models of leukodystrophy: a new perspective for the development of therapies
| Autor: | Noémie Hamilton, Holly A. Rutherford |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Nervous System Malformations Biochemistry Motor function Mice 03 medical and health sciences Autoimmune Diseases of the Nervous System 0302 clinical medicine Leukoencephalopathies White matter degeneration Animals Humans Medicine Cognitive Dysfunction In patient Cognitive decline Adrenoleukodystrophy Molecular Biology Zebrafish business.industry Perspective (graphical) Leukodystrophy Leukodystrophy Metachromatic Cell Biology medicine.disease Alexander disease Leukodystrophy Globoid Cell Metachromatic leukodystrophy Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Alexander Disease business Neuroscience |
| Zdroj: | The FEBS Journal. 286:4176-4191 |
| ISSN: | 1742-4658 1742-464X |
| Popis: | The leukodystrophies are a family of heritable disorders characterised by white matter degeneration, accompanied by variable clinical symptoms including loss of motor function and cognitive decline. Now thought to include over 50 distinct disorders, there are a vast array of mechanisms underlying the pathology of these monogenic conditions and, accordingly, a range of animal models relating to each disorder. While both murine and zebrafish models continue to aid in the development of potential therapies, many of these models fail to truly recapitulate the human condition - thus leaving substantial weaknesses in our understanding of leukodystrophy pathogenesis. Additionally, the heterogeneity in leukodystrophy presentation - both in patients and in vivo models - often results in a narrow focus on single disorders in isolation across much of the literature. Thus, this review aims to synthesise prominent research regarding the most common leukodystrophies in order to provide an overview of key animal models and their utility in developing novel treatments. We begin by discussing the ongoing revolution across the leukodystrophy field following the rise of next generation sequencing, before focusing more extensively on existing animal models from the mouse and zebrafish fields. Finally, we explore how these preclinical models have shaped the development of therapeutic strategies currently in development. We propose future directions for the field and suggest a more critical view of the dogma which has underpinned leukodystrophy research for decades. |
| Databáze: | OpenAIRE |
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