Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation

Topic: Brain proteins, microglia and lab models

Plain-language summary

The presynaptic protein alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease. First, two missense mutations A30P and A53T cause inheritable early onset Parkinson's disease in some families. Secondly, alpha-synuclein is present in Lewy bodies of affected nerve cells in the predominant sporadic type of Parkinson's disease as well as in dementia with Lewy bodies. We demonstrate in the rat optic system that a portion of alpha-synuclein is carried by the vesicle-moving fast component of axonal transport and that it binds to rat brain vesicles through its amino-terminal repeat region. We find alpha-synuclein with the A30P mutation of familial Parkinson's disease devoid of vesicle-binding activity and propose that mutant alpha-synuclein may accumulate, leading to assembly into Lewy body filaments.

@article{jensen1998-9756856,
  author  = {Jensen, P. H. and Nielsen, M. S. and Jakes, R. and Dotti, C. G. and Goedert, M.},
  title   = {{Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation}},
  journal = {The Journal of biological chemistry},
  year    = {1998},
  doi     = {10.1074/jbc.273.41.26292},
  pmid    = {9756856},
  url     = {https://doi.org/10.1074/jbc.273.41.26292}
}

Key findings

• The presynaptic protein alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease.
• First, two missense mutations A30P and A53T cause inheritable early onset Parkinson's disease in some families.
• Secondly, alpha-synuclein is present in Lewy bodies of affected nerve cells in the predominant sporadic type of Parkinson's disease as well as in dementia with Lewy bodies.
• We demonstrate in the rat optic system that a portion of alpha-synuclein is carried by the vesicle-moving fast component of axonal transport and that it binds to rat brain vesicles through its amino-terminal repeat region.
• We find alpha-synuclein with the A30P mutation of familial Parkinson's disease devoid of vesicle-binding activity and propose that mutant alpha-synuclein may accumulate, leading to assembly into Lewy body filaments.

Why it matters

In the rat optic system, alpha-synuclein bound to brain vesicles, and the A30P familial Parkinson's disease mutation abolished this binding. The authors propose that mutant alpha-synuclein may accumulate and form Lewy body filaments, but this is laboratory work and not a treatment.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1074/jbc.273.41.26292
• PubMed: 9756856
• Original source →
• Free full text: Journal of Biological Chemistry →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

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