Table 1.

Evidence supporting a role for nucleolar dysfunction in neurological disorders

DISORDER	EVIDENCE OF NUCLEOLAR DYSFUNCTION
	Morphological	Biochemical	Genetic/Epigenetic
Alzheimer’s Disease	Reduced nucleolar size in the cerebro-cortical, hippocampal and Meynert’s nucleus neurons [85–87, 99]	Increased oxidation of rRNA and ribosomal failure in the hippocampus and/or cerebral cortex [88–90]	CpG hypermethylation of the rDNA promoter in the cerebral cortex [91]
ANE Syndrome	–a	–	Inactivating mutation of the nucleolar LSU biogenesis factor RBM28 cause the disease [59]
Bowen-Conradi Syndrome	–	–	Inactivating mutation of the nucleolar SSU biogenesis factor EMG1 causes the disease [58]
Cockayne Syndrome	–	–	Inactivating mutations of the NER mediators and Pol1 co-factors CSB, XPBb and XPDc cause the disease ([61] and references therein).
Huntington’s Disease (HD)	–	–	Reduced nucleolar transcription and levels/activity of the nucleolar transcription factor UBFd in a mouse striatal cell line with an HD-associated mutation in the mouse Htte and in the striatum of transgenic mice overexpressing an HD mutant fragment of human HTT (R6/2 mouse line) [23].
Parkinson’s Disease	Reduction in nucleolar size and the nucleolar marker B23 in nigral neurons of PD patients [75, 100]	–	Mouse nigral neuron degeneration following dopaminergic-neuron-specific knock out of the Pol1 co-activator TIF1A [75]
Prader-Willi Syndrome (PWS)	Reduced nucleolar size in neurons from PWS patients and transgenic mice with the PWS-like paternal deficiency of gene expression [66]	–	Microdeletions within the chromosome 15 PWS region that selectively disrupt the snoRNA gene cluster SNORD116 (HBII-85) are sufficient to causes the key features of the disease [62, 63]
Rett Syndrome	Reduced nucleolar size in the Mecp2 mouse knockout model of Rett syndrome [68]	–	–
Suicide with history of abuse in childhood	–	Reduced levels of 18S rRNA in the hippocampus of affected individuals [101]	CpG hypermethylation of the rDNA promoter in the hippocampus ofaffected individuals [101]

^ano data available;

^bXPB, xeroderma pigmentosum group B;

^cXPD, xeroderma pigmentosum group D;

^dUBF, upstream binding factor;

^eHTT, huntingtin