Lysosomal Storage Diseases

Alroy, Joseph; Lyons, Jeremiah A.

doi:10.1177/2326409813517663

Cited by 30 publications

(48 citation statements)

References 24 publications

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“…Obwohl die lysosomalen Speicherkrankheiten (LSK [1]), wie fast alle erblichen Stoffwechselstörungen, heute molekulargenetisch, allenfalls biochemisch diagnostiziert werden, verbleibt ein diagnostisches Potenzial auch für den Pathologen, der erste Hinweise auf eine LSK geben kann, z. B. im Frühstadium einer LSK, das bisweilen schon im intrauterinen Zeitraum als Hydrops fetalis imponieren kann.…”

Section: Hintergrundunclassified

“…Da die morphologischen Veränderungen [1,2,4] bei LSK fast jeden Zell-und Gewebetyp -darunter z. B. epitheliale, mesenchymale Zellen, v. a. aber auch Neurone [4,12] und Glia, sowie Abschnitte peripherer einschließlich autonomer Nerven [4] -betreffen können, ist der hier bearbeitete Zugang über histiozytäre bzw.…”

Section: Morphologische Veränderungenunclassified

“…retikuloendotheliale Zellen nicht zwingend, dennoch sinnvoll, da diese Zellen bei einem Drittel bis der Hälfte der LSK oft richtungsweisende Veränderungen, "Speicherphänomene", zeigen, somit zu "Speicherzellen" transformiert sind. Der Kernpunkt der LSK, das Speicherlysosom, entsteht durch makro-oder mikroautophagische das primäre Lysosom einbeziehende [1,10], durch Substratspeicherung ausgelöste Prozesse, aus denen das sekundäre, speichernde Lysosom mit vielfälti-ger, teils bizarrer Ultrastruktur hervorgeht [1,2,4]. Die makroautophagische Schiene meint, dass in der Speicherzelle Membranbruchstücke anfallen können [12], die im Lysosomenäquivalent allmählich "ausgedünnt" werden, bis fast nur die nicht abbaubare Speichersubstanz übrigbleibt.…”

Section: Morphologische Veränderungenunclassified

“…Ein umfassenderer, systematischer, an Tiermodellen illustrierter Über-blick liegt in der neueren Literatur vor [1]. Aus Beschränkungsgründen sind in der Tabelle nicht alle Gruppen von LSK weiter differenziert, so nicht die Mukopolysaccharidosen [1] und die neuronalen Zeroidlipofuszinosen [4,11]. Insgesamt können nur einige "Schlaglichter" auf die Morphologie einiger Formen der LSK geworfen werden.…”

Section: Formen Und Unterformenunclassified

“…B. im Frühstadium einer LSK, das bisweilen schon im intrauterinen Zeitraum als Hydrops fetalis imponieren kann. Angesichts der Vielzahl der bekannten LSK, die weiter ansteigt und 50 Formen längst überschreitet [1,8], wird sich daran kaum etwas ändern, auch wenn bereits ganze Cluster von Genen auf einmal untersucht werden können. …”

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Lysosomale Speicherkrankheiten

Bornemann

Harzer

2015

Pathologe

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The pathologist may be the first to suspect LSD and this applies to LSDs that show storage histiocytes or one of a number of other LSDs in which only minor or absent storage is seen in histiocytes but marked storage phenomena are found in other cell systems. Some of the numerous, extremely heterogeneous LSDs may, however, be overlooked as detailed knowledge of the generally rare LSDs is the domain of LSD specialists. Clinicians, pathologists, geneticists and biochemists should cooperate in solving the diagnostic problems.

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Section: Hintergrundunclassified

Section: Morphologische Veränderungenunclassified

Section: Formen Und Unterformenunclassified

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Lysosomale Speicherkrankheiten

Bornemann

Harzer

2015

Pathologe

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Loss of Hsp67Bc leads to autolysosome enlargement in the Drosophila brain

Malkeyeva

Киселева

Федорова

2021

Cell Biology International

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Hsp67Bc is a small heat shock protein found in Drosophila melanogaster. Apart from performing a function (common for all small heat shock proteins) of preventing aggregation of misfolded proteins, it is involved in macroautophagy regulation alongside the Starvin protein. Overexpression of the D. melanogaster Hsp67Bc gene has been shown to stimulate macroautophagy in S2 cell culture. Nonetheless, it has been unknown how the absence of the Hsp67Bc gene may affect it. Here, we studied the effect of Hsp67Bc gene deletion on the macroautophagy induced by the pathogenic Wolbachia wMelPop strain in D. melanogaster. We detected Wolbachia inside autophagic vacuoles in fly neurons, thereby proving that these endosymbionts were being eliminated via macroautophagy. Nevertheless, we did not register any difference in brain bacterial load between Hsp67Bc-null and control flies at all tested stages of ontogenesis. Moreover, the abundance of autophagic vacuoles was similar between neurons of the mutant and control flies, yet the cross-sectional area of autolysosomes on ultrathin sections was more than 1.5-fold larger in Hsp67Bc-null fly brains than in the control line. Our findings suggest that the product of the Hsp67Bc gene does not participate in the initiation of endosymbiont-induced macroautophagy but may mediate autophagosome maturation: the deletion of the Hsp67Bc gene leads to the increase in autolysosome size.

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Chaperones as potential therapeutics for Krabbe disease

Graziano

Pannuzzo

Avola

et al. 2016

J of Neuroscience Research

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Krabbe's disease (KD) is an autosomal recessive, neurodegenerative disorder. It is classified among the lysosomal storage diseases (LSDs). It was first described in , but the genetic defect for the galactocerebrosidase (GALC) gene was not discovered until the beginning of the 1970s, 20 years before the GALC cloning. Recently, in 2011, the crystal structures of the GALC enzyme and the GALC-product complex were obtained. For this, compared with other LSDs, the research on possible therapeutic interventions is much more recent. Thus, it is not surprising that some treatment options are still under preclinical investigation, whereas their relevance for other pathologies of the same group has already been tested in clinical studies. This is specifically the case for pharmacological chaperone therapy (PCT), a promising strategy for selectively correcting defective protein folding and trafficking and for enhancing enzyme activity by small molecules. These compounds bind directly to a partially folded biosynthetic intermediate, stabilize the protein, and allow completion of the folding process to yield a functional protein. Here, we review the chaperones that have demonstrated potential therapeutics during preclinical studies for KD, underscoring the requirement to invigorate research for KD-addressed PCT that will benefit from recent insights into the molecular understanding of GALC structure, drug design, and development in cellular models. © 2016 Wiley Periodicals, Inc.

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Lysosomal Storage Diseases

Cited by 30 publications

References 24 publications

Lysosomale Speicherkrankheiten

Lysosomale Speicherkrankheiten

Loss of Hsp67Bc leads to autolysosome enlargement in the Drosophila brain

Chaperones as potential therapeutics for Krabbe disease

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