Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease

Buddhala, Chandana; Loftin, Susan K.; Kuley, Brandon M.; Cairns, Nigel J.; Campbell, Meghan C.; Perlmutter, Joel S.; Kotzbauer, Paul T.

doi:10.1002/acn3.246

Cited by 160 publications

(123 citation statements)

References 52 publications

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“…Furthermore, microbiota compositional changes can affect the immune system, GI epithelial cells and both glial cells and neurons in the nervous system 56 63–65. Changes in the composition of the gut microbiota can either precede or occur during Parkinson’s disease 66. Therefore, the authors speculate that the peripheral premotor symptoms of Parkinson’s disease may even originate from the intestine and demonstrate that alterations in microbiome composition can alter brain function 66…”

Section: Gut Dysbiosis and Altered Brain Functionmentioning

confidence: 98%

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

Arneth¹

2018

Postgraduate Medical Journal

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Section: Gut Dysbiosis and Altered Brain Functionmentioning

confidence: 98%

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

Arneth¹

2018

Postgraduate Medical Journal

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“…Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylethanol (DOPE), and 3,4-dihydroxyphenylalanine (DOPA) are mainly responsible for the structure of neuromelanin from substantia nigra, while noradrenaline, 3,4-dihydroxymandelic acid (DOMA), and 3,4-dihydroxyphenylethylene glycol (DOPEG) are responsible for the structure of neuromelanin from locus coeruleus [108]. Deficiencies in these monoamines are currently found in PD [109,110]. Monoamine transporters (MATs) that facilitate the reuptake of noradrenaline, dopamine, and serotonin are sodium-coupled transport proteins belonging to the neurotransmitter/Na + symporter (NSS) family, which have also been implicated in PD [111,112].…”

Section: Novel Treatmentsmentioning

confidence: 99%

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

Cacabelos

2017

IJMS

451

300

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Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.

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“…Cholinergic and dopaminergic denervation of the neocortex probably accounts at least in part for cognitive deficits in LBDs (24–29). Concomitant pathologies have also been suggested to explain variations in the degree of cognitive impairment in DLB (30–32).…”

Section: Introductionmentioning

confidence: 99%

Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms

et al. 2017

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ObjectivesThe goal of this study was to assess mitochondrial function, energy, and purine metabolism, protein synthesis machinery from the nucleolus to the ribosome, inflammation, and expression of newly identified ectopic olfactory receptors (ORs) and taste receptors (TASRs) in the frontal cortex of typical cases of dementia with Lewy bodies (DLB) and cases with rapid clinical course (rpDLB: 2 years or less) compared with middle-aged non-affected individuals, in order to learn about the biochemical abnormalities underlying Lewy body pathology.MethodsReal-time quantitative PCR, mitochondrial enzymatic assays, and analysis of β-amyloid, tau, and synuclein species were used.ResultsThe main alterations in DLB and rpDLB, which are more marked in the rapidly progressive forms, include (i) deregulated expression of several mRNAs and proteins of mitochondrial subunits, and reduced activity of complexes I, II, III, and IV of the mitochondrial respiratory chain; (ii) reduced expression of selected molecules involved in energy metabolism and increased expression of enzymes involved in purine metabolism; (iii) abnormal expression of nucleolar proteins, rRNA18S, genes encoding ribosomal proteins, and initiation factors of the transcription at the ribosome; (iv) discrete inflammation; and (v) marked deregulation of brain ORs and TASRs, respectively. Severe mitochondrial dysfunction involving activity of four complexes, minimal inflammatory responses, and dramatic altered expression of ORs and TASRs discriminate DLB from Alzheimer’s disease. Altered solubility and aggregation of α-synuclein, increased β-amyloid bound to membranes, and absence of soluble tau oligomers are common in DLB and rpDLB. Low levels of soluble β-amyloid are found in DLB. However, increased soluble β-amyloid 1–40 and β-amyloid 1–42, and increased TNFα mRNA and protein expression, distinguish rpDLB.ConclusionMolecular alterations in frontal cortex in DLB involve key biochemical pathways such as mitochondria and energy metabolism, protein synthesis, purine metabolism, among others and are accompanied by discrete innate inflammatory response.

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Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease

Cited by 160 publications

References 52 publications

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

Gut–brain axis biochemical signalling from the gastrointestinal tract to the central nervous system: gut dysbiosis and altered brain function

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

Dementia with Lewy Bodies: Molecular Pathology in the Frontal Cortex in Typical and Rapidly Progressive Forms

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