title: Spectral properties and mechanisms that underlie autofluorescent accumulations in Batten disease.
abstract: Neuronal Ceroid Lipofuscinoses (NCLs) have an incidence of 1 in 12,500 live births. These devastating neurodegenerative lysosomal storage diseases are characterized by the lysosomal accumulation of autofluorescent storage material (AFSM) similar to that seen in aging cells. Using patient derived lymphoblasts from three genetically distinct NCLs we report that AFSM for each NCL has distinct spectral properties. Moreover, by using pharmacological inhibitors to disrupt various biochemical pathways in normal control lymphoblasts we have determined that disruptions in microtubule assembly and non-muscle myosin II function results in accumulation of lysosomal AFSM. Interestingly, inhibition of autophagy did not result in AFSM. We conclude that cellular disturbances outside the lysosome in addition to compromised function of this organelle can result in accumulation of lysosomal AFSM in NCLs and possibly as a result of cellular aging.
authors.affiliation: Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Sabrina S
authors.initials: SS
authors.lastname: Seehafer
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000293:Adolescent; D000328:Adult; D016922:Cellular Senescence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005453:Fluorescence; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism* / Q000473:pathology*; D013050:Spectrometry, Fluorescence
chemical_list: D024462:Myosin Type II