Table 1.

NEAT1 expression in the CNS of patients and rodent models of neurodegenerative diseases.

Disease	NEAT levels (and how measured)	Where measured	Proposed role	Proposed mechanism(s)	References
Amyotrophic lateral sclerosis (ALS)	Up (qRT-PCR, in situ hybridisation). Confirmed NEAT1_2 upregulation.	Human: spinal motor neurons and glia Rodent: N/A	Protective	1Compensatory increase in NEAT1 expression and paraspeckle assembly due to compromised function of TDP-43 in miRNA biogenesis. 2Inflammatory response (activation of type I interferon signalling in TDP-43 depleted cells).	[30,109]
Frontotemporal dementia (FTD)	Up (iCLIP, qRT-PCR)	Human: brain (cortex) Rodent: N/A	Not known	Since NEAT1 levels were measured indirectly, TDP-43 binding to NEAT1 rather than the actual NEAT1 abundance could increase.	[111,115]
Huntington's disease (HD)	Up (microarrays, RNA-Seq, qRT-PCR)	Human: brain (caudate) Rodent: R6/2 mouse model; brain	Protective	MeCP2 protein represses NEAT1_2 under normal conditions; in HD, MeCP2 becomes downregulated which leads to NEAT1_2 accumulation.	[[118], [119], [120], [121], [122], [123]]
Parkinson's disease (PD)	Up (microarrays)	Human: brain (substantia nigra) Rodent: MPTP mouse model; midbrain	Detrimental	NEAT1 stabilises the PD-associated protein PINK1 and promotes PINK1-mediated autophagy.	[127,128]
Alzheimer's disease (AD)	Up (microarrays; RNA-Seq, qRT-PCR)	Human: hippocampus, entorhinal cortex, middle temporal gyrus, posterior cingulate cortex, superior frontal gyrus Rodent: N/A	Protective	NEAT1 positively regulates miR-15/107 which decreases CDK5R1 expression.	[[133], [134], [135]]
Epilepsy	Up (in humans; in rats - acute downregulation). Both isoforms are increased, with different temporal dynamics (qRT-PCR, in situ hybridisation)	Human: cerebral cortex (neocortex, low and high activity regions) Rodent: rat models of pilocarpine or kainic acid-induced epilepsy (temporal lobe epilepsy)	Dual	1NEAT1 controls the transcription of genes encoding ion channel components. 2NEAT1 interacts with the potassium channel-interacting protein KCNAB2, which adjusts the activity of ion channels and the excitatory response.	[29,89,90]
Traumatic brain injury (TBI)	Up (qRT-PCR)	Human: cerebral cortex Rodent: N/A	Protective	Regulation of the inflammatory response following injury. NEAT1 overexpression reduces the production of IL-1β, TNF-α and nitric oxide and protects cells via regulation of apoptosis.	[63,138]