Familial Dysautonomia: Mechanisms and Models.

Abstract:

:Hereditary Sensory and Autonomic Neuropathies (HSANs) compose a heterogeneous group of genetic disorders characterized by sensory and autonomic dysfunctions. Familial Dysautonomia (FD), also known as HSAN III, is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population. The major features of the disease are already present at birth and are attributed to abnormal development and progressive degeneration of the sensory and autonomic nervous systems. Despite clinical interventions, the disease is inevitably fatal. FD is caused by a point mutation in intron 20 of the IKBKAP gene that results in severe reduction in expression of IKAP, its encoded protein. In vitro and in vivo studies have shown that IKAP is involved in multiple intracellular processes, and suggest that failed target innervation and/or impaired neurotrophic retrograde transport are the primary causes of neuronal cell death in FD. However, FD is far more complex, and appears to affect several other organs and systems in addition to the peripheral nervous system. With the recent generation of mouse models that recapitulate the molecular and pathological features of the disease, it is now possible to further investigate the mechanisms underlying different aspects of the disorder, and to test novel therapeutic strategies.

journal_name

Genet Mol Biol

authors

Dietrich P,Dragatsis I

doi

10.1590/1678-4685-GMB-2015-0335

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

497-514

issue

4

eissn

1415-4757

issn

1678-4685

pii

S1415-47572016005009103

journal_volume

39

pub_type

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