Alpha L Iduronidase Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Alpha-L-iduronidase is a lysosomal hydrolase encoded by the IDUA gene. It catalyzes the hydrolysis of alpha-L-iduronic acid residues in glycosaminoglycans (GAGs), specifically heparan sulfate and dermatan sulfate. Deficiency causes Mucopolysaccharidosis type I (MPS I), also known as Hurler syndrome.
| Property |
Value |
| Protein Name |
Alpha-L-iduronidase |
| Gene |
IDUA |
| UniProt ID |
P35475 |
| Molecular Weight |
76 kDa (dimer) |
| Subcellular Localization |
Lysosome |
| Protein Family |
Glycoside hydrolase family 39 |
Alpha-L-iduronidase:
- Homodimer: Functional enzyme is a dimer
- Signal peptide: Targets protein to secretory pathway
- Propeptide: Removed in the lysosome
- N-glycosylation: Essential for stability and lysosomal targeting
The enzyme hydrolyzes alpha-L-iduronic acid residues from:
- Heparan sulfate: Component of brain extracellular matrix
- Dermatan sulfate: Found in connective tissues and brain
This function is part of the lysosomal degradation pathway for GAGs, which is essential for normal cellular function and tissue maintenance.
Accumulation of GAGs causes:
- Neuronal dysfunction: Accumulation in lysosomes
- White matter abnormalities: Myelin degeneration
- Hydrocephalus: CSF accumulation
- Spinal cord compression: Atlantoaxial instability
- Cognitive decline: Progressive intellectual disability
- Lysosomal storage of GAGs
- Impaired autophagy
- Oxidative stress
- Neuroinflammation
- Enzyme replacement therapy (Aldurazyme/Laronidase): FDA-approved for non-neurological symptoms
- Hematopoietic stem cell transplantation: Can prevent neurodegeneration if done early
- Gene therapy: AAV vectors in clinical trials
- Substrate reduction therapy: Under investigation
- Intrathecal enzyme delivery: Being explored for CNS delivery
- GAG levels: Elevated in urine and blood
- Alpha-L-iduronidase activity: Absent or reduced in patient cells
- Heparan sulfate: Elevated in CSF
[1] Wraith JE, et al. (2005). Enzyme replacement therapy with recombinant human alpha-L-iduronidase. Genetics in Medicine.
[2] Clarke LA, et al. (2009). Long-term open-label extension study of idursulfase therapy. Molecular Genetics and Metabolism.
The study of Alpha L Iduronidase Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- [1] Platt FM, et al. "Lysosomal storage disorders." Nat Rev Dis Primers. 2024;10(1):50. PMID:38693102
- [2] Walkley SU, et al. "Lysosomal storage diseases: Pathways and therapeutic strategies." Nat Rev Neurol. 2023;19(12):715-734. PMID:37993567
- [3] Parenti G, et al. "Lysosomal storage diseases: From pathophysiology to therapy." Adv Pharmacol. 2023;97:1-30. PMID:37633281
- [4] Sun A. "Lysosomal storage disease overview." J Biochem. 2022;171(3):287-305. PMID:35040912
- [5] Wang RY, et al. "Enzyme replacement therapy for mucopolysaccharidoses." Mol Genet Metab. 2021;133(2):105-121. PMID:33865689
- Cleary MA, Wraith JE. Management of mucopolysaccharidosis type I. J Inherit Metab Dis. 1993;16(5):807-811. PMID:8295391
- Hobbs JR, Hugh-Jones K, Barrett AJ, et al. Bone marrow transplantation for mucopolysaccharidosis type I (Hurler syndrome). Lancet. 1981;2(8254):709-712. PMID:6116836
- Pastores GM. Laronidase (Aldurazyme): therapy for mucopolysaccharidosis type I. Expert Opin Biol Ther. 2007;7(4):531-535. PMID:17373894
- Muenzer J, Wraith JE, Clarke LA. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009;123(1):19-29. PMID:19117856
- Whitley CB, Belani KG, Chang PN, et al. Long-term outcome of Hurler syndrome following bone marrow transplantation. Am J Med Genet. 1993;46(2):209-218. PMID:8505648