Fig. 5

Mechanisms of multifunctional neuroprotection through PSC-CM. Oxidative stress alters SOD1 activity, and dysfunctional or mutant SOD1 causes further oxidative damage; this induces apoptosis, destabilizes mitochondria and promotes hyperinflammation. Distinct PSC-CM proteins through different mechanisms have the capacity to act together to attenuate ROS, improve proteostasis, inhibit Cas3 activation and apoptosis, and promote neuronal repair. The key candidates in PSC-CM as neuroprotective factors are TIMP1, ApoE, ANG, ANG1, and HSP27, whose neuroprotective effects have been confirmed in literature. Ultimately, PSC-CM delays or inhibits death and denervation of MNs, promoting muscle innervation and preventing degeneration. Figure created using BioRender (https://biorender.com/)