Parkinson's disease and the gut: a well known clinical association in need of an effective cure and explanation.
Parkinson's disease (PD) is a neurodegenerative disorder which leads to severe movement impairment; however, Parkinsonian patients frequently suffer from gastrointestinal (GI) problems which at present are poorly understood, scarcely investigated, and lack an effective cure. Traditionally, PD is attributed to the loss of mesencephalic dopamine-containing neurons; nonetheless, additional nuclei, such as the dorsal motor nucleus of the vagus nerve and specific central noradrenergic nuclei, are now identified as targets of PD. While the effects of PD on the somatic motor systems are well characterized, the influence on the digestive system still needs to be clarified. Recent findings demonstrate the occurrence of pathological alterations within peripheral neuronal networks in the GI tract of Parkinsonian patients. However, it remains unclear whether a real cell loss occurs, and whether this happens specifically for a subclass of autonomic neurons or if it reflects the sole loss of autonomic nerves. This review summarizes the neurochemical and morphological changes which might be responsible for impaired GI motility. Moreover, we focus on the experimental models to reproduce the altered digestive system of Parkinsonian patients since an experimental model able to mimic such features of PD is required. In the last part of the manuscript, we suggest potential therapeutic targets.
Natale
G
G
Department of Human Morphology and Applied Biology, University of Pisa, Italy.
Pasquali
L
L
Ruggieri
S
S
Paparelli
A
A
Fornai
F
F
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism; D018492:Dopamine Antagonists / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000628:therapy; D005769:Gastrointestinal Motility / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000502:physiology*; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D018377:Neurotransmitter Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine