Table 3.

Summary of piRNAs aberrantly expressed in neural processes and 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]
Neuropathic pain	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]

Abbreviations: PA14 Pseudomonas aeruginosa, SNPs Single nucleotide polymorphisms, CNS Central nervous system, LINE1 Long interspersed nuclear elements, DNMT3a DNA methyltransferase 3A