Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain

Rohn, Troy T.; Catlin, Lindsey W.

doi:10.1371/journal.pone.0020495

Cited by 50 publications

(41 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 The data presented demonstrate an increased risk of nigral degeneration and clinical parkinsonian signs in the birth cohort potentially exposed to the influenza virus at a critical age for development of Von Economo’s encephalitis, although none had documented clinical infection at this time. Recently, Rohn and colleagues have discovered the influenza A virus on macrophages in addition to the presence of T cells within the substantia nigra pars compacta (SNpc) from postmortem PD brain sections 20 , further supporting the possible link between idiopathic PD and viral inflammatory causes.…”

Section: Discussionmentioning

confidence: 97%

Substantia nigra depigmentation and exposure to encephalitis lethargica

Hack

Jicha

Abell

et al. 2012

Annals of Neurology

View full text Add to dashboard Cite

Objective Parkinsonism has been occasionally reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900’s. Methods The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of SN depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. Substantia nigra (SN) depigmentation, detected neuropathologically, was correlated with clinical parameters of PD, age, and birth cohort. Results SN depigmentation was detected in 57 (13.2%) of the cohort. While qualitative SN depigmentation correlated modestly with age (p=0.02), it correlated best with birth cohort (p=0.009) for women born in the years 1895–1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890–1894 and 1900–1904 (p≤0.001). SN depigmentation correlated with speed of 6 and 50 foot walk (p<0.0001), “up and go” (p<0.0001), and hand coordination (p<0.0001). Interpretation Subjects in the birth cohort 1895–1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons that were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica.

show abstract

Section: Discussionmentioning

confidence: 97%

Substantia nigra depigmentation and exposure to encephalitis lethargica

Hack

Jicha

Abell

et al. 2012

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Macroautophagy appears to be implicated in PD pathogenesis since several key proteins driving this cellular process are deregulated. Beclin‐1, which is responsible for the formation and the maturation of autophagosomes, is increased in the SN of PD patients (Rohn and Catlin ; Miki et al . ), as well as LC3II (Dehay et al .…”

Section: Abnormal Protein Removal and Degradationmentioning

confidence: 99%

Molecular changes in the postmortem parkinsonian brain

Toulorge

Schapira²,

Hajj

2016

Journal of Neurochemistry

View full text Add to dashboard Cite

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by 'reverse biochemistry' i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD.

show abstract

“…Moreover, diseases like asthma and seasonal and allergic rhinitis might be associated with PD [124], suggesting that chronic rhinitis, i.e., rhinitis-related inflammation, might promote the entry of neurotropic pathogens via the olfactory route [79]. Interestingly, influenza A virus has been detected in the SNpc of PD brains [125], and the interferon-induced protein MxA, which plays a role in defense against influenza virus, is associated with LBs [126] . …”

Section: Spread Of Synucleinopathy and Progression Of Parkinson’s Dismentioning

confidence: 99%

Inflammation and α-Synuclein’s Prion-like Behavior in Parkinson's Disease—Is There a Link?

et al. 2012

View full text Add to dashboard Cite

Parkinson’s disease patients exhibit progressive spreading of aggregated α-synuclein in the nervous system. This slow process follows a specific pattern in an inflamed tissue environment. Recent research suggests that prion-like mechanisms contribute to the propagation of α-synuclein pathology. Little is known about factors that might affect the prion-like behavior of misfolded α-synuclein. In this review, we suggest that neuroinflammation plays an important role. We discuss causes of inflammation in the olfactory bulb and gastrointestinal tract and how this may promote the initial misfolding and aggregation of α-synuclein, which might set in motion events that lead to Parkinson's disease neuropathology. We propose that neuroinflammation promotes the prion-like behavior of α-synuclein and that novel anti-inflammatory therapies targeting this mechanism could slow disease progression.

show abstract

Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain

Cited by 50 publications

References 30 publications

Substantia nigra depigmentation and exposure to encephalitis lethargica

Substantia nigra depigmentation and exposure to encephalitis lethargica

Molecular changes in the postmortem parkinsonian brain

Inflammation and α-Synuclein’s Prion-like Behavior in Parkinson's Disease—Is There a Link?

Contact Info

Product

Resources

About