A lot of compounds are known and available to modulate (inhibit or activate) the most prominent mode of programmed cell death – Apoptosis. In a recent post, I summarized methods to detect early Apoptosis and at the end of this post you’ll find a list of apoptosis modulators (available through tebu-bio). But there are other modes of programmed cell death, such as Autophagy (see How to manipulate and measure Autophagy), Necroptosis, and Ferroptosis.

Today I would like to focus on Ferroptosis, and invite you to take a look at the first Ferroptosis inhibitor on the market.

Fig. 1: Process of Apoptosis

Apoptosis is the most prominent process of programmed cell death (for an overview see Fig. 1). Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. Furthermore, changes affecting the membrane, nucleus, cytoplasm, and mitochondria occur. Apoptosis involves a complex cascade of reactions regulated by specific proteases called caspases (take a look at previous posts on Caspases as pharmaceutical targets – how to screen for inhibitors?), and results in DNA degradation. Apoptotic processes have been researched in an extensive variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer.

Besides apoptosis other types of programed cell death are known, such as autophagy (see How to manipulate and measure Autophagy?), necroptosis, and ferroptosis (look out for an imminent post I’ll be doing about this iron-dependent form of cell death very shortly, as well as tools to differentiate between apoptois, necroptosis, autophagy, and ferroptosis).

In this post, let’s take a look at methods and kits allowing to measure early apoptotic events.

In a recent post I gave an overview about the role of Caspases in different human diseases and introduced tools to measure Caspase activity and inhibition by compounds in homogenous biochemical assays: Caspases as pharmaceutical targets – how to screen for inhibitors? Today I would like to give you an overview about a method and kits which allow to detect active Caspases in cells and which give an insight into the apoptotic status of the respective cells. Hence the effects of inducers of apoptosis can be investigated in living cells.

Caspases (cysteine-dependent aspartate-directed proteases) belong to the family of cysteine proteases and are involved in networks controlling cell death (apoptosis and necrosis) and inflammation. 12 human caspases have been described so far (1.). Human Caspases have been classified according to their roles in apoptosis (Caspase-3, -6, -7, -8, and -9) and inflammation (Caspase-1, -4, -5, and -12). Caspase-2, -10, and -14 can be less easily classified concerning the function (for an overview see 2.).

So let’s take a further look at their role, and some of the tools available to investigate and screen compounds modifying Caspase activities.