Relaxin-3

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Structure of relaxin-3
Relaxin-3 neurons in the mouse nucleus incertus
Distribution of relaxin-3 neurons and projections

Relaxin-3 is a

endogenously
, are currently unknown).

Structure

Relaxin-3 consists of 51

disulfide bonds (two interchain, one intrachain), with the residues that mediate binding to/activation of RXFP3 residing within the B-chain. At translation, pro-relaxin-3 also contains a C-chain (in between the A and B-chains) which is removed via protolytic cleavage to form the mature neuropeptide.[3]

Distribution

Relaxin-3 is mostly expressed within

axons where it can be detected in presynaptic vesicles before release onto target neurons, characteristic of a neurotransmitter.[4] The largest number of relaxin-3-positive neurons in the rodent brain are within a region of the pontine brainstem known as the nucleus incertus,[5] while smaller populations are present within the pontine raphe, periaqueductal grey, and an area dorsal to the substantia nigra. From these centres, relaxin-3 innervates a broad range of brain regions which are also rich in RXFP3 mRNA/binding sites, including the extended limbic system and the septohippocampal pathway.[6][7]

Function

The broad distribution of relaxin-3 fibres/RXFP3 within several key neuronal circuits suggests an ability to modulate a broad range of behaviours. This has been confirmed in a growing number of rodent studies, which demonstrate relaxin-3 is able to modulate arousal, the response to stress, feeding/metabolism and memory; and likely plays a role in the generation/regulation of hippocampal theta rhythm.[8]

Relevance to human disease

Neuropeptides such as relaxin-3 are attracting increasing interest as targets for the pharmacological treatment of a range of neuropsychiatric diseases. Due to the ability of relaxin-3 to modulate neuronal processes/behaviours such as mood, stress responses and cognition, which are often aberrant in mental illnesses, considerable potential exists for the development of relaxin-3-based drugs to therapeutically treat depression and other mental illnesses.

See also

References

  1. PMID 11689565
    .
  2. PMID 15707501
    .
  3. PMID 16365033
    .
  4. S2CID 24594286
    .
  5. S2CID 24464719
    .
  6. S2CID 11971485
    .
  7. S2CID 42656023
    .
  8. S2CID 9589579
    .
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