The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Desp...The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,and caffeine.Despite a few studies investigating biomarkers to rgeting molecular pathways different from alpha-synuclein in Parkinson's disease,these results should be replicated and observed in studies on larger cohorts,considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes.Although the need fo r standardization in sample collection and processing,salivary-based biomarkers studies have reported encouraging results,calling for large-scale longitudinal studies and multicentric assessments,given the great molecular potentials and the non-invasive accessibility of saliva.展开更多
文摘The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,and caffeine.Despite a few studies investigating biomarkers to rgeting molecular pathways different from alpha-synuclein in Parkinson's disease,these results should be replicated and observed in studies on larger cohorts,considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes.Although the need fo r standardization in sample collection and processing,salivary-based biomarkers studies have reported encouraging results,calling for large-scale longitudinal studies and multicentric assessments,given the great molecular potentials and the non-invasive accessibility of saliva.
