p53 in neurodegenerative diseases and brain cancers

Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson’s disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway

“…Among miR-34 family (miR34a, miR-34b and miR-34c), miR-34b and miR-34c share a common host gene location that is different from miR-34a [26]. All miR-34 family members are direct targets of p53, while both histological and biological evidence concur to taking place in PD [27]. Therefore, the different dysregulation of miR-34a or miR-34b/ c can be contributed to complicated p53 networks.…”

Putting p53 in Context

“…In an accelerated process, patients with the heritable DNA repair deficiency syndrome Fanconi anemia hyperactivate p53 in response to unresolved DNA damage and eventually experience bone marrow failure owing to progressive HSC loss (Ceccaldi et al, 2012). Excessive p53-dependent apoptosis can also drive developmental disorders of the brain (Houlihan and Feng, 2014) and aging-associated neurodegenerative diseases, namely Alzheimer’s and Parkinson’s diseases (reviewed in Checler and Alves da Costa, 2014). As a regulator of cell death, p53 has been implicated in the pathological response to cerebral and cardiac ischemia; p53 inhibition has been proposed as a protective strategy in the acute phase following injury (Gudkov and Komarova, 2010).…”

Autophagy and p53

“…Again, whether autophagy restrains p53 activity or whether this neurodegeneration is p53 dependent is not known and will be interesting to test. Augmented p53 activity does underlie some brain abnormalities, neurologic dysfunction, and neurodegeneration (Trimmer et al 1996; Morrison et al 2003; Bae et al 2005; Terzian et al 2007; Checler and Alves da Costa 2014; Zhang et al 2014), raising the possibility that restraining p53 by autophagy in this setting may be important to prevent tissue damage and organismal death.…”