Journal ArticleDOI
Non-human primate models of PD to test novel therapies
Marc Morissette,Thérèse Di Paolo +1 more
TLDR
Non-human primate models of Parkinson disease show many similarities with the human disease and have been useful to seek new drug targets, since they reproduce motor complications observed in parkinsonian patients as reviewed here.Abstract:
Non-human primate (NHP) models of Parkinson disease show many similarities with the human disease. They are very useful to test novel pharmacotherapies as reviewed here. The various NHP models of this disease are described with their characteristics including the macaque, the marmoset, and the squirrel monkey models. Lesion-induced and genetic models are described. There is no drug to slow, delay, stop, or cure Parkinson disease; available treatments are symptomatic. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-Dopa) still remains the gold standard symptomatic treatment of Parkinson. However, involuntary movements termed L-Dopa-induced dyskinesias appear in most patients after chronic treatment and may become disabling. Dyskinesias are very difficult to manage and there is only amantadine approved providing only a modest benefit. In this respect, NHP models have been useful to seek new drug targets, since they reproduce motor complications observed in parkinsonian patients. Therapies to treat motor symptoms in NHP models are reviewed with a discussion of their translational value to humans. Disease-modifying treatments tested in NHP are reviewed as well as surgical treatments. Many biochemical changes in the brain of post-mortem Parkinson disease patients with dyskinesias are reviewed and compare well with those observed in NHP models. Non-motor symptoms can be categorized into psychiatric, autonomic, and sensory symptoms. These symptoms are present in most parkinsonian patients and are already installed many years before the pre-motor phase of the disease. The translational usefulness of NHP models of Parkinson is discussed for non-motor symptoms.read more
Citations
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MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)
Ronald B. Postuma,Daniela Berg +1 more
TL;DR: The International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease as discussed by the authors have been proposed for clinical diagnosis, which are intended for use in clinical research, but may also be used to guide clinical diagnosis.
Journal ArticleDOI
Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs.
TL;DR: The challenges associated with the development of novel therapies for Parkinson disease are discussed, highlighting emerging agents that aim to target cell death, as well as new targets offering a symptomatic approach to managing features and progression of the disease.
Journal Article
Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Discussion
TL;DR: Observations that NMDA receptor antagonists injected into the striatum or given systemically have the ability to act palliatively or prophylactically to alleviate levodopa-induced response alterations support the view that sensitization of striatal NMDA receptors contributes to the pathogenesis of motor dysfunction in Parkinson's disease.
Journal ArticleDOI
Microglial Implication in Parkinson's Disease: Loss of Beneficial Physiological Roles or Gain of Inflammatory Functions?
Cynthia Lecours,Maude Bordeleau,Maude Bordeleau,Léo Cantin,Martin Parent,Thérèse Di Paolo,Marie-Ève Tremblay +6 more
TL;DR: The literature discussing the functional and morphological changes that microglia undergo in PD pathophysiology and upon exposure to its two main environmental risk factors, aging, and chronic stress are summarized.
Journal ArticleDOI
Advances in Parkinson's Disease: 200 Years Later.
Natalia Lopez-Gonzalez del Rey,Ana Quiroga-Varela,Elisa Garbayo,Iria Carballo-Carbajal,Rubén Fernández-Santiago,Mariana H G Monje,Ines Trigo-Damas,María J. Blanco-Prieto,Javier Blesa +8 more
TL;DR: Some of the key advances in the field over the past two centuries are highlighted and the current challenges focusing on exciting new research developments likely to come in the next few years are discussed.
References
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Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
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