title: Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases.
abstract: Lysosomal storage diseases are inherited metabolic disorders caused by genetic defects causing deficiency of various lysosomal proteins, and resultant accumulation of non-degraded compounds. They are multisystemic diseases, and in most of them (>70%) severe brain dysfunctions are evident. However, expression of various phenotypes in particular diseases is extremely variable, from non-neuronopathic to severely neurodegenerative in the deficiency of the same enzyme. Although all lysosomal storage diseases are monogenic, clear genotype-phenotype correlations occur only in some cases. In this article, we present an overview on various factors and processes, both general and specific for certain disorders, that can significantly modulate expression of phenotypes in these diseases. On the basis of recent reports describing studies on both animal models and clinical data, we propose a hypothesis that efficiency of production of compounds that cannot be degraded due to enzyme deficiency might be especially important in modulation of phenotypes of patients suffering from lysosomal storage diseases.
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gabig-Cimińska
authors.forename: Zyta
authors.initials: Z
authors.lastname: Banecka-Majkutewicz
authors.forename: Bogdan
authors.initials: B
authors.lastname: Banecki
authors.forename: Alicja
authors.initials: A
authors.lastname: Węgrzyn
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
mesh_terms: D000818:Animals; D001519:Behavior / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004798:Enzymes / Q000235:genetics / Q000502:physiology; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D020140:Lysosomal Storage Diseases, Nervous System / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D008247:Lysosomes / Q000201:enzymology; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D019683:Penetrance; D010641:Phenotype
chemical_list: D004798:Enzymes