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Review
. 2021 Dec;16(12):2390-2392.
doi: 10.4103/1673-5374.313031.

Caspase-1: an important player and possible target for repair of the blood-brain barrier underlying neurodegeneration

Daniel Rand  1 , Itzik Cooper  2
Affiliations
Review

Caspase-1: an important player and possible target for repair of the blood-brain barrier underlying neurodegeneration

Daniel Rand et al. Neural Regen Res. 2021 Dec.
No abstract available

PubMed Disclaimer

Conflict of interest statement

None

Figures

Figure 1
Figure 1
BBB breakdown and caspase-1 activation. (A) BBB and NVU structure: brain capillaries that constitute the BBB. Endothelial cells are ensheathed with astrocytes end-feet and pericytes. Isolated brain capillaries are shown (green, lectin; blue, nuclei). Bar: 10 µm. (B) BBB breakdown may be mediated and/or aggravated through blood-borne toxins/metabolic disorders/life style/genetics. It can also be initiated from within the brain, and it is often a vicious cycle in which BEC and other brain cells impact each other, promoting cell stress that ultimately leads to neuronal degeneration and dysfunction. Some examples of BBB-related damage are illustrated: 1: Dysregulated receptor and transporter expression levels and/or function that can lead to decreased clearance of toxic molecules such as amyloid β; 2: Caveolae-mediated transport might be dysregulated, promoting molecules and cell dyshomeostasis; 3, 4: Activation of BEC (by pathogens, toxins etc.) leads to immune cell activation, adhesion to BEC, and extravasation to the brain. Tight junctions and adherens junction protein degradation enables paracellular gaps and increased transport of toxic molecules and cells to the brain; 5: Brain cells such as pericytes, astrocytes and microglia can release pro-inflammatory cytokines as a result of various stimuli and promote BEC damage/activation, and vice versa; 6: BEC injury can lead to cell apoptosis and death; 7, 8: Blood-derived molecules and red blood cells cross the damaged BBB and injure brain parenchyma by releasing injurious molecules such as Fe+2 and ROS. (C) Caspase-1 is activated after various stimuli by the assembly of inflammasomes. We propose attempting to target the compromised BBB by inhibiting caspase-1, which has shown a multifaceted repair ability in BEC. The examples illustrated here are generalized to account for multiple CNS diseases in which the BBB is disrupted. ASC: Apoptosis-associated speck-like protein containing a caspase recruitment domain; BBB: blood-brain barrier; BEC: brain endothelial cells; CNS: central nervous system; IL: interleukin; NVU: neurovascular unit; ROS: reactive oxygen species.
See this image and copyright information in PMC

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