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      Determinants of dopaminergic neuron loss in Parkinson's disease

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      The FEBS Journal
      Wiley

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          Abstract

          <p class="first" id="P1">The cardinal motor symptoms of Parkinson’s disease (PD) are caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Alpha-synuclein (aSYN) pathology and mitochondrial dysfunction have been implicated in PD pathogenesis, but until recently it was unclear why SNc dopaminergic neurons should be particularly vulnerable to these two types of insult. In this brief review, the evidence that SNc dopaminergic neurons have an anatomical, physiological and biochemical phenotype that predisposes them to mitochondrial dysfunction and synuclein pathology is summarized. The recognition that certain traits may predispose neurons to PD-linked pathology creates translational opportunities for slowing or stopping disease progression. </p><p id="P2">This review summarizes evidence that selective neuronal vulnerability in Parkinson’s disease results from several phenotypic traits: 1) calcium-dependent, feed-forward control of mitochondrial respiration leading to elevated reactive oxygen species and cytosolic calcium concentration; 2) an extensive axonal arbor; and 3) a reactive neurotransmitter. These traits increase vulnerability to genetic mutations associated with PD, age and environmental toxins. </p><p id="P3"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/8122478c-007f-4743-b9ec-7cc45ed78121/PubMedCentral/image/nihms-982631-f0001.jpg"/> </div> </p>

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          Author and article information

          Journal
          The FEBS Journal
          FEBS J
          Wiley
          1742464X
          October 2018
          October 2018
          August 14 2018
          : 285
          : 19
          : 3657-3668
          Affiliations
          [1 ]Department of Physiology; Feinberg School of Medicine; Northwestern University; Chicago IL USA
          Article
          10.1111/febs.14607
          6546423
          30028088
          efd37e58-a11c-4620-882e-1b19250be256
          © 2018

          http://doi.wiley.com/10.1002/tdm_license_1.1

          http://onlinelibrary.wiley.com/termsAndConditions#vor

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