Review Article

Could Proteomic Research Deliver the Next Generation of Treatments for Pneumococcal Meningitis?

Table 3

Poteins associated with the apoptotic pathway could potentially be discovered in the CSF after cell death. The levels of these proteins can be expected to increase during pneumococcal meningitis as a result of both the inflammatory response and the release of pneumococcal proteins.

ProteinDescriptionActionReferences

Cytochrome C (Cyt C)A small heme protein found loosely associated with the inner membrane of the mitochondrionCause ER calcium release. The overall increase in calcium triggers a massive release of additional cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the inositol 3 phosphate receptors. This release in turn activates caspase-9[66]
Tumour necrosis factor (TNF-α)TNF acts via the TNF receptor (TNF-R) and is part of the extrinsic pathway for triggering apoptosisTNF-R associates with procaspases through adapter proteins (FADD, TRADD, etc.)[67]
CaspasesProteases, which exist as inactive proenzymesPlay essential roles in apoptosis (programmed cell death) and inflammation[10]
FasLigand which associated with the forms the Death Inducing Signalling Complex (DISC) upon ligand bindingFas pathway is sufficient to induce complete apoptosis in certain cell types through DISC assembly and subsequent caspase-8 activation[68]
Fas-associated death domain protein (FADD)An adaptor molecule that bridges the Fas-receptor, and other death receptors, to caspase-8 through its death domainForms the death inducing signalling complex (DISC) during apoptosis[68]
BAXA proapoptotic member of the Bcl-2 protein familyActivated Bax forms an oligomeric pore in the outer membrane[10]
Apoptosis inducing factor (AIF)A flavoprotein found in the mitochondrial intermembrane space in healthy cellsEssential for nuclear disassembly in apoptotic cells[10]