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**21** 

*Italy* 

Tommaso Beccari et al.\*

*Dipartimento di SEEA, Università di Perugia,* 

**Role of Lysosomal Enzymes in Parkinson's** 

The lysosome, initially discovered by Christian de Duve in 1955, is an intracellular organelle responsible of the ordered degradation of proteins, glycoproteins, proteoglycans, lipids, and other macromolecules originated from autophagy, endocytosis and phagocytosis. It is characterize by a limiting external membrane containing intraluminal vesicles. These organelles are estimated to contain 50-60 soluble acidic hydrolases (Journet et al., 2002), 55 membrane-associated proteins and 215 integral membrane proteins (Bagshaw et al., 2005). The macromolecules are scomposed by acid hydrolases in small molecules that are transported back in the cytosol by specific transporter proteins and then catabolized or reused by anabolic processes. Lysosomal hydrolases are synthetized as N-glycosylated precursors in the endoplasmatic reticulum and are transported to the lysosomes via a vectorial transport dependent on mannose 6-phosphate. Lysosomes are involved in many cellular processes like cholesterol homeostasis, autophagy, membrane repair, pathogen defense, cell signaling, apoptosys and bone/tissue remodelling; it is a foundamental organelle for cell life and not only the wastebasket of the cell. Microscopic identification of lysosomes is hard due to heterogeneity of organelles morphology dependent on their function as digestive organelles. The size and quantity of lysosomes varies in different cell types and can increase when the lysosomes accumulate non-digested material. Functional deficit of hydrolases, membrane-associated or integral membrane proteins causes lysosomal storage disorders (LSDs), a group of inherited metabolic pathologies characterized by intralysosomal deposition of undegraded macromolecules and by multisystemic phenotype (Saftig, 2006). The absence or reduced activity of a specific lysosomal hydrolase or other lysosomal proteins cause an abnormal function of the entire endosomal/lysosomal system

More than 50 lysosomal storage disorders (LSD) are known with a total incidence of 1:7,000- 1:9,000 (Fletcher, 2006). Two thirds of them involve the central nervous system (Meikle et al.,

\*Chiara Balducci1, Silvia Paciotti1, Emanuele Persichetti1, Davide Chiasserini2, Anna Castrioto2, Nicola Tambasco2, Aroldo Rossi2, Paolo Calabresi2, Veronica Pagliardini3, Bruno Bembi4 and

*2Clinica Neurologica, Ospedale S. Maria della Misericordia, Università di Perugia, Italy* 

*3Dipartimento di Pediatria, Università di Torino, Italy 4Centro Regionale per le malattie Rare, Ospedale Universitario 'Santa Maria della Misericordia', Italy* 

**1. Introduction** 

(Bellettato & Scarpa, 2010).

*1Dipartimento di SEEA, Università di Perugia, Italy*

Lucilla Parnetti2

**Disease: Lesson from Gaucher's Disease** 

