Emerging role of autophagy in pediatric neurodegenerative and neurometabolic diseases.

[alexander disease]

Pediatric neurodegenerative diseases are a heterogeneous group of diseases that result from specific genetic and biochemical defects . In recent years , studies have revealed a wide spectrum of abnormal cellular functions that include impaired proteolysis , abnormal lipid trafficking , accumulation of lysosomal content , and mitochondrial dysfunction . Within neurons , elaborated degradation pathways such as the ubiquitin-proteasome system and the autophagy-lysosomal pathway are critical for maintaining homeostasis and normal cell function . Recent evidence suggests a pivotal role for autophagy in major adult and pediatric neurodegenerative diseases . We herein review genetic , pathological , and molecular evidence for the emerging link between autophagy dysfunction and lysosomal storage disorders such as Niemann-Pick type C , progressive myoclonic epilepsies such as Lafora disease , and leukodystrophies such as Alexander disease . We also discuss the recent discovery of genetically deranged autophagy in Vici syndrome , a multisystem disorder , and the implications for the role of autophagy in development and disease . Deciphering the exact mechanism by which autophagy contributes to disease pathology may open novel therapeutic avenues to treat neurodegeneration . To this end , an outlook on novel therapeutic approaches targeting autophagy concludes this review .

Diseases
Validation

Diseases presenting "wide spectrum" symptom

22q11.2 deletion syndrome

acute rheumatic fever

adrenal incidentaloma

adrenomyeloneuropathy

alexander disease

allergic bronchopulmonary aspergillosis

canavan disease

classical phenylketonuria

focal myositis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

krabbe disease

lamellar ichthyosis

monosomy 21

neonatal adrenoleukodystrophy

oligodontia

primary hyperoxaluria type 1

proteus syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

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