Inside into the role of heparan sulfate and dopamine as disease' modifiers in Mucopolysaccharidosis type IIIA (DSB.AD005.112)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Istituto di Biochimica e Biologia Cellulare (IBBC)

Project manager

ELVIRA DE LEONIBUS
Phone number: 0690091
Email: elvira.deleonibus@cnr.it

Abstract

MPS-IIIA is due to the loss of the gene that codifies for arylsulfatase B, a lysosomal enzyme that degrades the glycosaminoglycan (GAG) heparan sulfate (HS). The lysosome is responsible for cell clearance of misfolded proteins and physiological catabolism of cell components such as GAGs. In MPS-IIIA, undegraded HS accumulates in the lysosome, progressively engulfing it and damaging its degradative capacity, leading to the accumulation of secondary storages composed of misfolded proteins such as alpha-synuclein, tau and beta-amyloid; the latter are protein aggregates responsible for neurodegeneration in age-related neurodegenerative disorders. The loss of function of the lysosome is therefore considered as the primary cause of neurodegeneration in MPS-IIIA, responsible for the dementia that occurs at the latest stage of the disease.

In the early stage of the disease, however, MPS-IIIA manifests with severe autistic-like symptoms (hyperactivity, stereotyped behaviors etc.), which poorly respond to dopaminergic D2 receptors antagonist drugs, such as risperidone and haloperidol. Supported by previous grants from MPS, Cure Sanfilippo and Sanfilippo Children Foundation, we have found th

Start date of activity

22/10/2021

Keywords

rare diseases, dopamine, neurodegeneration

Last update: 18/02/2025