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The Threshold Theory for Parkinson's Disease.

Simone Engelender1, Ole Isacson2

  • 1Department of Biochemistry, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.

Trends in Neurosciences
|November 30, 2016
PubMed
Summary

We propose a new threshold theory for Parkinson's disease (PD), suggesting parallel nervous system degeneration. This theory better explains PD symptom progression than the ascending propagation model.

Keywords:
Parkinson's diseasedopaminergic neuronsfunctional thresholdspreading theoryα-synuclein

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Area of Science:

  • Neuroscience
  • Neurology
  • Pathology

Background:

  • Parkinson's disease (PD) is characterized by alpha-synuclein accumulation in neurons.
  • Current theories propose alpha-synuclein propagation from neuron to neuron.
  • The Braak's hypothesis suggests a peripheral nervous system (PNS) to central nervous system (CNS) ascent of pathology.

Purpose of the Study:

  • To propose a novel threshold theory for Parkinson's disease.
  • To challenge the ascending propagation theory of alpha-synuclein.
  • To provide an alternative explanation for PD neurobiology and symptom progression.

Main Methods:

  • Review and synthesis of existing neurobiological evidence for PD.
  • Comparative analysis of the threshold theory versus the ascending theory.
  • Examination of the functional reserve of motor control systems.

Main Results:

  • Evidence suggests parallel degeneration in both the CNS and PNS in PD.
  • A lower functional threshold exists for early PD symptoms, preceding motor deficits.
  • The midbrain dopamine and basal ganglia systems possess significant functional reserve.

Conclusions:

  • The proposed threshold theory offers a more comprehensive explanation for PD.
  • Parallel degeneration in CNS and PNS better fits observed PD progression.
  • The threshold theory provides a superior framework compared to Braak's hypothesis.