Common Pathways to Neurodegeneration and Co-morbid Depression

  • Darcy Litteljohn
  • Emily Mangano
  • Shawn HayleyEmail author


Depression is highly co-morbid with a number of neurodegenerative conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke and multiple sclerosis. Although psychosocial stress and impairment play a substantial role, accumulating evidence suggests that co-morbid depressive illness may emerge from alterations in processes related to the primary neurodegenerative condition. For instance, depression in PD may occur long before motor disability and in many cases is likely related to early degeneration in brainstem or limbic regions. We posit that pro-inflammatory cytokines and their associated inflammatory signaling pathways (e.g., JAK-STAT, NFκB, and MAP kinases), as well as other immuno-inflammatory factors such as the microglial inducible enzyme, cyclooxygenase-2 (COX-2), may play a primary role in modulating the emergence of co-morbid depression. In this regard, neuroprotective/neurotrophic anti-inflammatory factors may have important antidepressant properties. The present review will cover the evidence concerning the mechanisms through which depression might emerge in PD and other neurodegenerative disorders. Secondly, we will focus on the important cytokines, inflammatory co-factors and intracellular signaling proteins that could be targeted to potentially provide therapeutic benefit for depression as well as the primary neurodegenerative condition.


Parkinson’s disease Depression Co-morbidity Inflammation Cytokine Cyclooxygenase 



5-hydroxytryptamine (serotonin)


serotonin-transporter-linked polymorphic region




arachidonic acid


Alzheimer’s disease


blood brain barrier


B-cell lymphoma-2


brain-derived neurotrophic factor


cyclic adenosine monophosphate


central nervous system




cAMP response element-binding protein


corticotrophin-releasing hormone


cerebrospinal fluid




docosahexaenoic acid


glial cell line-derived neurotrophic factor


indoleamine 2,3-dioxygenase


interleukin-converting enzyme






insulin-like growth factor


inhibitor of kappaB




inducible nitric oxide synthase


janus kinase


c-Jun N-terminal kinase


leucine rich repeat kinase 2




mitogen-activated protein kinase


middle cerebral artery occlusion


major histocompatibility complex


manganese superoxide dismutase




messenger ribonucleic acid


nicotinamide adenine dinucleotide phosphate




nuclear factor kappaB


nerve growth factor


N-methyl D-aspartate


nitric oxide


nonsteroidal anti-inflammatory drug


Parkinson’s disease




reactive oxygen species


substantia nigra pars compacta


signal transducer and activator of transcription


transforming growth factor


T helper type-1


tumor necrosis factor-alpha


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Institute of NeuroscienceCarleton UniversityOttawaCanada

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