Neurotensin Pathways and Their Role in Central Nervous System Disorders

Neurotensin is a tridecapeptide neurotransmitter and neuromodulator widely expressed in the central nervous system. Synthesised primarily in hypothalamic and brainstem nuclei, it exerts its effects via three receptors: the high-affinity G protein-coupled receptor NTSR1, the lower-affinity NTSR2, and the non-G protein-coupled sortilin (NTSR3). Within the CNS, neurotensin modulates dopaminergic, serotonergic, GABAergic, glutamatergic and cholinergic circuits, influencing reward, motor control, pain perception and neuroendocrine regulation. Dysregulation of neurotensin signalling has been implicated in the pathophysiology of schizophrenia, where alterations in dopaminergic tone are central, and in movement disorders such as Parkinson’s disease, where neuroprotective and trophic effects are under investigation. Moreover, neurotensin pathways contribute to the modulation of nociceptive transmission in chronic pain states and to the central control of appetite and metabolic homeostasis. Advances in receptor pharmacology have spawned novel peptide analogues and small-molecule modulators aimed at fine-tuning neurotensin receptor activity, with therapeutic potential in psychiatric, neurodegenerative and pain disorders. Ongoing research seeks to unravel the precise intracellular signalling cascades, receptor dimerisation events and cross-talk with other neurotransmitter systems that underlie both physiological functions and pathological processes.

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Neurotensin Pathways and Their Role in Central Nervous System Disorders publication trend

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Technical terms

Neurotensin: A 13-amino-acid peptide acting as neurotransmitter and neuromodulator in the brain.

NTSR1 (Neurotensin Receptor 1): A high-affinity G protein-coupled receptor mediating most rapid neurotensin effects.

Neuromodulator: A substance that modifies or regulates neural circuit activity without directly eliciting excitatory or inhibitory postsynaptic potentials.

Dopaminergic system: Neural pathways employing dopamine, central to motor control, reward and psychiatric function.

References

1. The Isolation of a New Hypotensive Peptide, Neurotensin, from Bovine Hypothalami. Journal of Biological Chemistry (1973).
2. The 100-kDa Neurotensin Receptor Is gp95/Sortilin, A Non-G-Protein-coupled Receptor*. Journal of Biological Chemistry (1998).
3. Diverse Roles of Neurotensin Agonists in the Central Nervous System. Frontiers in Endocrinology (2013).