|
aSyn (therapeutic) antibody
| {Trudler, 2021 #2028} | hiPSC-derived microglia | aSyn-antibody complexes enhanced rather than suppressed inflammasome-mediated IL-1β secretion |
Comorbidity
| IL-1β ↑? | Reference / Finding | ||
|---|---|---|---|
| RA | RA → (anti-inflammatory drugs) → ↓ PD ? | yes | {Bacelis, 2021 #1906}
|
| NSAID | NSAID → ↓ PD ? | No. |
|
| DM | PD → DM ? | Yes | {Lu, 2014 #1911}
|
| No | {Becker, 2008 #1912}
The study population encompassed 7,274 subjects (3,637 Parkinson's disease case subjects and 3,637 matched subjects in the comparison group free of Parkinson's disease).
| ||
| CVD | PD → CVD ? | yes | {Hong, 2018 #1913} meta-analysis
|
| yes | {Park, 2020 #1914} https://www.heart.org/idc/groups/heart-public/@wcm/@sop/@smd/documents/downloadable/ucm_483970.pdf For the 60-79-year-old age group, the following have HBP: Men: 67.0% of women. HBP: For the 65-74-year-old age group, the following have high blood pressure: 67.8% of women. Heart failure: For the 60-79 year-old age group, the following have heart failure: 7.8% of men, 4.5% of women. | ||
| {Rothman, 2020 #1916} Lack of effect of canakinumab compared to placebo on blood pressure | |||
| {Dalekos, 1997 #1917} 약 군당 30, 30.7 (24.2)) | |||
| {Alhusseiny, 2016 #1919} 고혈압약 IL-1β 의 변화 없음 (수술 환자 4 군 비교임). ODEWUSI, 2019: il-18 도 치료 & 동반 증가 | |||
| {Kempuraj, 2017 #1920}
*Cytokines/chemokines and other peripheral inflammatory molecules have been shown to cross BBB by an active transport mechanism (Banks et al., 1995) or through neurovascular coupling that lack BBB (Petrovic et al., 1995) or through circumventricular organs that lack BBB The peripheral immune and inflammatory mediators can interact with brain BBB endothelial cells and induce the release of additional inflammatory molecules including PGE₂ into the brain (Ek et al., 2001). Systemic immune cells such as T cells can infiltrate into the brain through the BBB via choroid plexus or CSF that could induce neurodegeneration (Ransohoff et al., 2003; Park et al., 2016). Peripheral inflammation is also translated to the brain through the vagus nerve by neural reflex (Tracey, 2009). As the BBB is disrupted in many neurological diseases, the trafficking of peripheral inflammatory cells/molecules across the BBB is increased and thereby increases neuroinflammation (Kortekaas et al., 2005; Takeda et al., 2013). Several previous reports indicate that mast cell activation (Karagkouni et al., 2013; Zhang et al., 2016), as well as peripheral inflammation influences BBB disruption to increase the permeability of inflammatory mediators and immune cell infiltration into the brain thereby spreading peripheral inflammation into the brain (Takeda et al., 2013). Peripheral inflammation due to LPS injection causes a significant increase in inflammatory cytokines/chemokines, suggesting/indicating neuroinflammation could occur without increasing the AB level in the brain (Takeda et al., 2013). A recent article reported that immunotherapy which selectively targets a specific T cell or microglial subset, can also improve cognitive impairment in AD patients and indicates the contribution of immune system in mediating brain inflammation in AD patients (Goldeck et al., 2016). Activated microglia and astrocytes release inflammatory mediators, which enter the peripheral system through the defective BBB and recruit immune cells to the brain, thereby exacerbating neuroinflammatory mechanisms (Streit et al., 2014; Goldmann et al., 2016). The brain was originally considered as an immunologically privileged organ but now it is well known that the peripheral immune system and the brain communicate through several pathways (Ransohoff and Brown, 2012). We have previously shown that the presence of a tumor in the AD patients increases peripheral neuroinflammation (Acquadro et al., 2014). Several peripheral inflammatory conditions (Figure 1) could activate mast cells and release proinflammatory and neurotoxic mediators such as GMF, α-syn, CRP, and chemokines. These molecules can also activate glia and neurons in the regulation of the neuroinflammatory mechanism. | |||
|
The peripheral immune and inflammatory mediators can interact with brain BBB endothelial cells and induce the release of additional inflammatory mediators. Further peripheral mast cells (located in dura mater and visceral organs near the BBB) can secrete additional inflammatory mediators including GMF and neuroinflammatory mediators including CXC chemokines. CCP expression, and induce neuronal damage and neurodegeneration. Furthermore, glia and mast cells reactivate each other in the brain through co-stimulatory molecules CD40/CD154 or inflammatory mediators such as TNF-α, IL-1β, IL-33. Mast cells and tryptase can affect endothelial cell tight junctions through PAR2. Mast cells can be reactivated by IL-33 with feedback in mediators in an autocrine and paracrine manner through Fcγ R activation, indicating neuroinflammatory pathways. α-syn release from mast cells, microglia and astrocytes generates neuroinflammatory mediators in PD patients and others. α-syn levels are reported to be increased in PD patient's brain. Once α-syn from connective tissue can alter BBB, enter the brain, and recruit immune and inflammatory cells through Toll-like receptor (TLR2) and Fcγ receptor pathways. Inflammatory mediators released from activated mast cells, microglia and astrocytes generate neuroinflammatory cytokines and immune cells to the brain. Differential genetic predisposing factors on neuroinflammation could be either inherited or acquired through environmental factors. Differential extent of mast cell activation, much like the situation where some mast cells located in dura mater and visceral organs of people with allergic reactions to a given place, even though all people living in that area are exposed to the same external environment such as pollen or dust at the spring. Additionally, the severity of allergic reactions also varies in these people. Another example is the variant metastasis to the brain. Metastasis of cancer also varies from person to person based on the immune condition of patients. This is because, most likely, the spread and the extent of mast cell activation-mediated disease severity also varies from person to person.
| |||
| {Banks, 1995 #1922} Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal fluid and interstitial fluid spaces of the brain and spinal cord. The brain efflux system enables transport of these cytokines and chemokines from blood to that of other water-soluble compounds. | |||
| esity | {Thornton, 2024 #2680}
| ||
Summary (sento M)
| Is IL-1b increased in this condition? | What is the prevalence of this condition in non-PD generalnormal poplation? | Does PD patients have increased prevalence of this in HC? | |
|---|---|---|---|
| 8% | {Becker et al., 2008, PMID 18559656}: 3,637 Parkinson's disease case subjects and 3,637 matched subjects in the comparison group free of Parkinson's disease).
| ||
| (Dalekos et al. 1997, PMID 9042815) ↑ (7x vs HC) IL-1b of HBP (d=1.38) | HBP: For the 65-74-year-old age group, the following have high blood pressure: 62.0% of women. (https://www.heart.org/idc/groups/heart-public/@wcm/@sop/) | {Hong et al. 2018, PMID 30021249} meta-analysis
|
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
Comorbidity / RA / 8,256 Parkinson's patients | reads In total, 8,256 Parkinson's patients with long-term follow-up data and without comorbidities — other medical conditions — were first matched with 82,452 controls; preserved verbatim. | low confidence on 82,452. |
CVD / Park, 2020 #1914 / 67.0% of women | reads Men: 67.0% of women; the gender column appears mismatched in source. | low confidence on column attribution. |
Kempuraj 2017 #1920 long paragraph / Acquadro et al., 2014 | the citation appears as (Acquadro et al., 2014) in this transcription though source spelling may differ; preserved verbatim. | low confidence on Acquadro spelling. |
Summary (sento M) / Dalekos et al. 1997 / 7x vs HC | reads ↑ (7x vs HC) IL-1b of HBP (d=1.38); preserved verbatim. | low confidence on Cohen’s d value. |
Comorbidity / esity / NT-0249 and NT-0796 | reads as written; the cell label esity is the visible-clipped suffix of Obesity. | edge truncation. |