Regional alpha-synuclein aggregation, dopaminergic dysregulation, and the development of drug-related visual hallucinations in Parkinson's disease.
Visual hallucinations in Parkinson's disease are usually treatment-related and occur in at least 30% of patients. Although their clinical and epidemiological features have been extensively reviewed, their etiopathogenesis remains a matter of debate. Based on the current evidence available, this review suggests that regional neurodegeneration of the ventral dopaminergic pathway, as evident in the aggregation of the protein alpha-synuclein, is the main event linked to the development of visual hallucinations in Parkinson's disease. Denervation supersensitivity of dopaminergic receptors in ventral striatal and mesocorticolimbic areas as well as defective synaptic buffering ability due to the loss of dopaminergic presynaptic terminals and dopamine transporter may be among the key factors leading to visual hallucinations in Parkinson's disease.
Papapetropoulos
Spiridon
S
Department of Neurology, University of Miami, Miller School of Medicine, Rm. 4004, 1501 NW 9th Ave., FL 33136, USA. spapapetropoulos@med.miami.edu
D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology; D006212:Hallucinations / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D008636:Mesencephalon / Q000187:drug effects / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D051844:alpha-Synuclein / Q000378:metabolism*
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic; C497604:SNCA protein, human; D051844:alpha-Synuclein; D004298:Dopamine