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Table 3 Summary of piRNAs aberrantly expressed in neural processes and diseases

From: An old weapon with a new function: PIWI-interacting RNAs in neurodegenerative diseases

Process or disease Category of piRNA Mechanism Animals/subjects Reference
Neural development 172 piRNAs expressed piRNAs regulate dendritic spine development Mouse [5]
Neural development PIWIL1 protein PIWIL1 promotes the multipolar morphology to the bipolar transition in cortex neurons Mouse [133]
Axonal regeneration piRNA-like sncRNAs (piLRNAs) MIWI/piLRNA complex attenuates axonal regeneration in rat sciatic nerve after crush injury Rat [134]
Axonal regeneration 3447 piRNAs upregulated, 4117 piRNAs downregulated MIWI-piRNA complex participates in Schwann cell responses to nerve injury Mouse [135]
Axonal regeneration piRNA pathway piRNA pathway inhibits axonal regrowth dependent on PIWI protein PRG-1 C. elegans [13]
Memory formation Abundant expression of 28-nt piRNAs Piwi/piRNA complex promotes serotonin-dependent methylation in the CREB2 promoter Aplysia [136]
Memory formation PIWIL1 and PIWIL2 Knockdown of Piwil1 and Piwil2 enhances contextual fear memory Mouse [137]
Memory formation PIWI protein less abundant in αβ mushroom body neurons Transposon inserts in αβ neurons, including insertion into memory-relevant loci Drosophila [138]
Memory formation piRNAs significantly changed after worm exposure to PA14 PIWI/PRG-1 is required for the induction of daf-7 expression in ASI neurons and induces the nuclear RNAi pathway in the transgenerational inheritance of learned pathogen avoidance behavior C. elegans [139, 140]
AD 81 piRNAs upregulated, 22 piRNAs downregulated piRNAs are nominally correlated with the genome-wide significant risk SNPs Prefrontal cortex from AD patients [11]
AD 146 piRNAs upregulated, 3 piRNAs downregulated piRNA targets focus on the 5 most significant AD-associated pathways enriched with 4 genes regulated by 4 piRNAs AD patient brain [12]
AD Depletion of piRNAs Depletion of piRNAs would drive transposable element dysregulation that leads to tauopathy neurodegeneration Drosophila [15]
PD piRNAs deregulation Massive deregulation of piRNAs in neuronal cells Sporadic PD- derived neuronal cells [14]
ALS Aub overexpression Caz knockdown increases pre-piRNA levels, but reduces mature-size piRNA levels in the central nervous system Drosophila [141]
Stroke 54 piRNAs upregulated, 51 piRNAs downregulated Transcription factors control stroke-responsive piRNAs in a redundant manner Rat [142]
Rett Syndrome piRNAs increased in Mecp2-knockout mouse cerebellum Upregulated transposons in Rett syndrome may lead to the increase of total piRNAs Mouse [143]
piRNA-DQ541777 piR-DQ541777 recruits DNMT3a to increase methylation of Cdk5rap1 promoter during neuropathic pain Mouse [144]
Anxiety Mili knockout Knockout of Mili induces LINE1 promoter hypomethylation in mouse brain and reduces anxiety-like behavior Mouse [145]
  1. Abbreviations: PA14 Pseudomonas aeruginosa, SNPs Single nucleotide polymorphisms, CNS Central nervous system, LINE1 Long interspersed nuclear elements, DNMT3a DNA methyltransferase 3A