Lysosomal Disorders

Abstract

Lysosomal storage disorders are a group of over 50 different genetic diseases that result from lysosomal dysfunction. This disruption of lysosomal function can involve either a specific lysosomal hydrolase deficiency, a defect in lysosomal protein processing, or impaired lysosomal biogenesis. To appreciate the pathogenesis of lysosomal disorders fully, it is important to understand the dynamics of endosome–lysosome organelles, their capacity for the uptake and degradation of complex macromolecules, and how lysosomal biogenesis and hydrolysis are altered by substrate storage. The focus of this article will be on recognized lysosomal disorders and what is known about the composition and the function of endosome–lysosome organelles in these diseases. The lysosomal network will be discussed with a view to correlating the main site of endosome–lysosome degradation and the site of substrate accumulation in lysosomal disorders. A major unanswered question for lysosomal storage disorders is how an enzyme deficiency and the resulting storage of undegraded macromolecules impact on cells to cause organ dysfunction and disease.

Élan VitalRevisited:Bergson and the Thermodynamic Paradigm

“…65 For Bergson, as we have seen, this is the élan vital, but others posit the large-scale directions, for example, of "maximum entropy production," 66 of "complexification," 67 or of "informational entropy production." 68 When it comes to positive accounts of these factors and their place in evolution, however, the theorists sharing this broad position differ among themselves. Probably the closest to Bergson's Creative Evolution would be Brooks and Wiley's unified theory of biology presented in Evolution as Entropy (1988).…”