Proteases lysosomal disorder

The neuronal ceroid lipofuscinoses (CLN), also referred to as Batten s disease, are a group of disorders characterized by the accumulation of autofluorescent lipopigments. Clinical hallmarks include blindness, seizures, cognitive and motor decline and early death. Age of onset varies from infancy to adulthood. Eight genetic forms have been identified [4]. Two involve lysosomal acid hydrolases. CLN1 codes for palmitoyl protein thioesterase 1. Clinically it presents most often in infancy and leads to loss of active movement and visual contact by 3 years of age. It is most common in Finland, where its incidence is 1 20,000. CLN2 codes for a lysosomal pepstatin-insensitive acid protease. 

Fig. 6. Model of the cellular pathways involved in generation of PrP. In the infectious manifestation of prion diseases, extracellular PrP in the form of a prion particle (1) interacts with PrP on the cell surface, possibly in detergent-resistant rafts, catalyzing its conversion to PrP (2). Conversion may also occur after uptake of the proteins into an endosomal compartment (3). Once formed, some PrP c accumulates in lysosomes (4), although the protein is probably found in a number of other cellular locations as well. In familial prion disorders, mutant PrP is converted spontaneously to the PrP state via a series of biochemical intermediates, the earliest of which is a PIPLC-resistant form generated in the ER (5). Mutant PrP molecules are subsequently delivered to the cell surface, where they become detergent-insoluble (6) and then protease-resistant (7), possibly in raft domains. Steps 6 and 7 could also occur in endocytic organelles. (Reprinted with permission from Harris, 1999).

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