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Axon degeneration in Parkinson's disease
Robert E Burke1, Karen O'Malley
1Department of Neurology, Columbia University, 650 W 168th St., New York, NY, 10032, USA. rb43@columbia.edu
Experimental Neurology
|January 31, 2012
Summary
Parkinson's disease (PD) research suggests focusing on axon degeneration, not just neuron cell bodies. Targeting these distinct mechanisms may offer new neuroprotection and restoration strategies for PD.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Cell Biology
Background:
- Parkinson's disease (PD) is a common neurodegenerative disorder affecting the basal ganglia.
- Current treatments do not halt PD progression; therapies often target neuron soma, assuming axon protection.
- Axon degeneration may precede other PD pathologies, making it a critical early intervention target.
Purpose of the Study:
- To propose a shift in neuroprotection strategies for PD towards targeting axon degeneration mechanisms.
- To review evidence supporting axon degeneration as an early feature of PD.
- To explore novel therapeutic targets and neurorestoration potential by focusing on axon biology.
Main Methods:
- Review of human post-mortem studies.
- Analysis of functional neuroimaging data.
- Examination of genetic causes and neurotoxin models of PD.
Main Results:
- Evidence suggests axon degeneration may be the earliest pathological event in PD.
- Molecular mechanisms of axon degeneration are distinct from those of neuron soma degeneration.
- Potential for axon regeneration in the central nervous system may be underestimated.
Conclusions:
- Focusing on the neurobiology of axons offers novel therapeutic opportunities for PD.
- Understanding axon degeneration pathways can lead to new neuroprotection strategies.
- Exploring axon growth potential opens avenues for neurorestoration in PD and other neurodegenerative diseases.
Keywords:
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-methyl-4-phenylpyridinium6-OHDA6-hydroxydopamineAAVADAVsAktAlzheimer's diseaseAutophagyDLBILBLBLRRK2Lewy bodyMFBMPP(+)MPTPPDParkinson's diseaseSNStriatumSubstantia nigraTHVMAT2Wallerian degeneration slowWld(S)[(3)H]TBZOHadeno-associated virusautophagic vacuolesdementia with Lewy Bodiesincidental Lewy bodiesleucine rich repeat kinase 2mTormedial forebrain bundlesubstantia nigratritiated α-dihydrotetrabenazinetyrosine hydroxylasevesicular monoamine transporterα-Synuclein
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