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Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson\u2019s disease (PD). Here we show that Hb confers DA cells\u2019 susceptibility to 1-methyl-4-phenylpyridinium (MPP<jats:sup>+<\/jats:sup>) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O<jats:sub>2<\/jats:sub> binding and is associated with insoluble aggregate formation in the nucleolus. Neurochemical stress induces epigenetic modifications, nucleolar alterations and autophagy inhibition that depend on Hb expression. When adeno-associated viruses carrying <jats:italic>\u03b1<\/jats:italic>- and <jats:italic>\u03b2<\/jats:italic>-chains of Hb are stereotaxically injected into mouse SN, Hb forms aggregates and causes motor learning impairment. 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