How were the cholinesterase inhibitors able to repigment hair?
In a study, Alzheimer's patients were given cholinesterase inhibitors for at least 6 months. It was found that some individuals had repigmentation of their grey hair. The cholinesterase inhibitors used were donepezil, rivastigmine, and galantamine. These drugs are used for Alzheimer's disease because the cholinergic functionality deteriorates with this disease. The researchers from the study above hypothesized that the grey hair was reversed because the cholinesterase inhibitors somehow induced melanogenesis.
Cholinesterase is an enzyme used to break down the neurotransmitter acetylcholine in the neuronal synapses. Acetylcholine is involved in various nervous system functions like memory, attention, ability to learn, muscle movements, etc. Cholinesterase inhibitors are drugs/compounds that prevent the breakdown of acetylcholine. This means that acetylcholine becomes abundant in the synapses.
In 2007, Hasse found that deleting the M4 muscarinic acetylcholine receptor had a profound negative impact on hair regeneration and hair pigmentation processes. These specific receptors can be found on melanocytes, keratinocytes, and in the hair follicles. This study shows that acetylcholine and hair pigment is linked, but it needs to be further explored.
What is the exact role that acetylcholine has in melanogenesis?
Use other cholinesterase inhibitors like physostigmine/eserine, tacrine, metrifonate, and see whether these other cholinesterase inhibitors can also reverse hair greying in humans!
In animal models observe how acetylcholine impacts melanogenesis on a cellular level.
If acetylcholine does have a major role in hair color then we could take advantage of this. We could repurpose cholinesterase inhibitors in the future to prevent hair greying or use other methods that achieve the same thing.
Chan, Luke Kar Man, et al. "Re‐pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population." Australasian Journal of Dermatology (2020).
Tabet, N. "Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing!." Age and ageing 35.4 (2006): 336-338.
Picciotto, Marina R., Michael J. Higley, and Yann S. Mineur. "Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior." Neuron 76.1 (2012): 116-129.
Sharma, Kamlesh. "Cholinesterase inhibitors as Alzheimer's therapeutics." Molecular medicine reports 20.2 (2019): 1479-1487.
Hasse, Sybille, et al. "The M4 muscarinic acetylcholine receptor plays a key role in the control of murine hair follicle cycling and pigmentation." Life sciences 80.24-25 (2007): 2248-2252.