Alpha 1-antitrypsin inhibits microglia activation and facilitates the survival of iPSC grafts in hypertension mouse model

CSF SerpinA1 in Creutzfeldt–Jakob disease and frontotemporal lobar degeneration

“…Alternatively, SerpinA1 post‐translational modifications might be detrimental by (1) blocking specific serine proteases and lead to impaired clearance of prion‐like proteins or (2) promoting the formation of a misfolded and self‐aggregate‐prone structure of SerpinA1 . On another issue, SerpinA1 is emerging as an important modulator of neuroinflammation …”

“…9,21 On another issue, SerpinA1 is emerging as an important modulator of neuroinflammation. [3][4][5] Independently from the hypothetical roles of SerpinA1, it seems that a different isoform-overexpression characterizes some of the CJD and FTLD subtypes. On the other hand, the preservation of the most abundant peak (number 3) in controls could suggest a possible critical physiological role of this isoform.…”

“…Another possible hypothesis could relate the different SerpinA1 patterns to the kinetics of the disease even if we did not find significant associations between the time from onset to LP and SerpinA1 signal in each CJD molecular subgroup. Moreover, given that SerpinA1 might play an anti‐inflammatory role by attenuating microglial activity, the increase in total SerpinA1 and in some of its isoforms in sCJD MM(V)1 compared to sCJD linked to PrP Sc type 2 could be considered a stronger early attempt to balance the developing neuroinflammation/neurodegeneration that progresses faster in the former group than in the latter. Possibly, SerpinA1 immunomodulation may attenuate during the slower disease course in VV2, MV2K, and MM2C cases.…”

“…In this regard, overexpression of the protein or its RNA has been described in the brains of patients with Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), suggesting that SerpinA1 overexpression may be detrimental to neuronal function . Moreover, the protein may play an anti‐inflammatory role by attenuating microglial activation, causing a reduction of neuroinflammation . It is also known that the protein might diffuse out of venous blood and be released from the brain tissue into the cerebrospinal fluid (CSF) .…”

“…1 Moreover, the protein may play an anti-inflammatory role by attenuating microglial activation, causing a reduction of neuroinflammation. [3][4][5] It is also known that the protein might diffuse out of venous blood and be released from the brain tissue into the cerebrospinal fluid (CSF). 6 Previous studies documented a higher concentration of CSF SerpinA1 and/or different levels of its charge isoforms in AD, Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies in comparison with controls.…”