English: Figure 4. Physiopathological events in GM2 gangliosidoses. Innate (IIR) and adaptative (AIR) immune response have been described in GM2 gangliosidoses. Upon the impaired of lysosomal degradation of the GM2 ganglioside, this can be released into the cytoplasm (a) where its sialic acid can interact with the rough endoplasmic reticulum (RER) (b). Sustained stress into RER induces the activation of proapoptotic proteins such as CHOP (c) that promotes mitochondrial-mediated apoptosis (d) In early apoptosis states, the phosphatidylserine (PS) is externalized (e), which promotes the recruitment of several proinflammatory cells such as microglia (f). Astrogliosis has also been reported in the GM2 gangliosidoses (g). The release of several astrocyte-derived cytokines (CK), such as CCL2 and CXCL10, increases the recruitment of microglia and the apoptosis in myelinating oligodendrocytes (AOD), which induces neuron demyelination (h). Finally, auto antibodies (Ab) against GM2 ganglioside seem to contribute to the physiopathology of the GM2 gangliosidoses (i), although the precise mechanism of its release has not described. ECC: Extracellular compartment, ICC: Intracellular compartment, AP: Apoptosome, OD: Oligodendrocyte.