Fig. 3

CK2 targets in neurodegenerative diseases. Red shapes denote targets that mediate CK2 pathological functions, blue shapes are proteins by which CK2 may exert a protective function against the disease, gray shapes indicate that the CK2-dependent phosphorylation has no disease-related effect. a Parkinson’s disease (PD): CK2 promotes α-synuclein aggregation in Lewis bodies (LB) by phosphorylating its Ser129, but this site is also target of other protein kinases. b Alzheimer’s disease (AD): CK2 is responsible for the 5-HT₄ receptor-stimulated induction of α-secretase activity, which in turn reduces the Aβ (amyloid β-peptide) production, through the non-amyloidogenic pathway of amyloid precursor protein (APP) processing. However, CK2 induces tau hyperphosphorylation, through the phosphorylation of SET, an inhibitor of the PP2A phosphatase, and its consequent cytosolic localization and binding to PP2A. Moreover, CK2 phosphorylates KLC 1, causing FAT impairment. Another AD-related CK2 target is PS-2, whose phosphorylation, however, does not affect the APP processing. c Huntington’s disease (HD): the HTT sites Ser13 and Ser16, found hypo-phosphorylated in the polyQ-HTT mutant, are increased by CK2 through a direct or indirect mechanism (dashed arrows), and this reduces cellular toxicity. d Spinocerebellar ataxia type 3 (SCA3): CK2 associates to and phosphorylates ataxin-3, thus promoting its nuclear localization and stabilization, and enhancing the formation of inclusions. e Amyotrophic lateral sclerosis (ALS): CK2 is a potential kinase of TDP43, the major component of protein aggregates in motor neurons, whose phosphorylation decreases its propensity to aggregate. Moreover, CK2 phosphorylates cyclin F, thus negatively controlling the E3 ligase activity of the SKP1/cullin1/F‐box (SCF)‐E3 ligase complex, and finally reducing the aberrant proteins ubiquitination typically observed in ALS