LeeLemonoil
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https://www.researchgate.net/public...processes_in_melanizedneuronal_and_skin_cells
Nice paper, discusses the putative effects of comon odorants on GPCRs.
ACtivation of these GPCRs by their odorant agonists might stop the downregulation of Neuromelanine in dopaminergic neurons amon others, thus be therapeutic in PDs and similar pathologies.
Pigmentation Disorders and
Neurodegenerative Diseases
The main source of dopamine in the brain is provided by
mesencephalic dopaminergic (mDA) neurons, consisting
essentially of two groups of projecting cells: the A9 neurons
of the substantia nigra (SN), that form the mesostriatal sys-
tem, and the A10 cells of the ventral tegmental area (VTA),
that constitute the mesocorticolimbic pathway (Ikemoto,
2007). These cells share many features including the enzy-
matic pathways involved in dopamine synthesis, release and
metabolism. ey also show common intrinsic electrophys-
iological properties such as spontaneous pacemaker activity
in the absence of synaptic inputs. SN neurons are involved
in regulating voluntary movements and postural reflexes,
whereas VTA cells play a fundamental part in reward and
attention. Dysfunction of mDA neurons has been implicat-
ed in several neurodegenerative disorders, such as selective
degeneration of A9 cells leading to Parkinson’s disease (PD)
(Grison et al., 2014). Besides the catecholaminergic neu-
rotransmitter type, the dopaminergic neurons of the SN
and the noradrenergic neurons of the locus coeruleus are
prominently characterized by their pigmentation, due to the
intraneuronal accumulation of neuromelanin (NM). NM is
a dark, non-autofluorescent polymeric pigment produced
almost exclusively in human catecholaminergic neurons,
mainly in the SN, whereas it is less generated in some oth-
er non-human primates, and it is absent from the brain in
many lower species (Fedorow et al., 2005). Function of NM
is considered to be especially protective, due to its ability
to chelate metals, mostly iron, the level of which increases
gradually with age. NM may also bind mitochondrial tox-
ins. Finally, it removes excess of cytosolic dopamine (DA)
not stored in synaptic vesicles, hence protecting the neuron
from oxidative stress related to DA autoxidation (Bobela et
al., 2015). In particular, in the cytosol of dopaminergic neu-
rons, DA can be oxidized via iron-mediated catalysis and
then react with β-sheets-structured proteins to form a mel-
anin-protein complex. During the polymerization process,
the melanin-protein conjugate can also bind high amounts of
metals, especially iron. e resulting NM is taken up into au-
tophagic vacuoles that subsequently fuse with lysosomes; here
NM interacts with lipids and proteins already present, thus
forming the mature NM-containing organelles. erefore, by
analogy with peripheral melanins, NM could function in vivo
to attenuate the eects of damaging stimuli, but, unlike mela-
nin in skin and retina, NM is not present in SN dopaminergic
neurons of humans during foetal development or at birth,
but develops over the rst few decades of life (Fedorow et al.,
2005). Further, human foetal dopamine neurons, when im-
planted as a treatment into the striatum of patients with PD,
exhibit a precocious production of the pigment. is supports
the concept that factors involved in neuronal maturation are
important for the production of NM
(PDF) Odorants could elicit repair processes in melanizedneuronal and skin cells. Available from: https://www.researchgate.net/public...processes_in_melanizedneuronal_and_skin_cells [accessed Dec 10 2018].
Nice paper, discusses the putative effects of comon odorants on GPCRs.
ACtivation of these GPCRs by their odorant agonists might stop the downregulation of Neuromelanine in dopaminergic neurons amon others, thus be therapeutic in PDs and similar pathologies.
Pigmentation Disorders and
Neurodegenerative Diseases
The main source of dopamine in the brain is provided by
mesencephalic dopaminergic (mDA) neurons, consisting
essentially of two groups of projecting cells: the A9 neurons
of the substantia nigra (SN), that form the mesostriatal sys-
tem, and the A10 cells of the ventral tegmental area (VTA),
that constitute the mesocorticolimbic pathway (Ikemoto,
2007). These cells share many features including the enzy-
matic pathways involved in dopamine synthesis, release and
metabolism. ey also show common intrinsic electrophys-
iological properties such as spontaneous pacemaker activity
in the absence of synaptic inputs. SN neurons are involved
in regulating voluntary movements and postural reflexes,
whereas VTA cells play a fundamental part in reward and
attention. Dysfunction of mDA neurons has been implicat-
ed in several neurodegenerative disorders, such as selective
degeneration of A9 cells leading to Parkinson’s disease (PD)
(Grison et al., 2014). Besides the catecholaminergic neu-
rotransmitter type, the dopaminergic neurons of the SN
and the noradrenergic neurons of the locus coeruleus are
prominently characterized by their pigmentation, due to the
intraneuronal accumulation of neuromelanin (NM). NM is
a dark, non-autofluorescent polymeric pigment produced
almost exclusively in human catecholaminergic neurons,
mainly in the SN, whereas it is less generated in some oth-
er non-human primates, and it is absent from the brain in
many lower species (Fedorow et al., 2005). Function of NM
is considered to be especially protective, due to its ability
to chelate metals, mostly iron, the level of which increases
gradually with age. NM may also bind mitochondrial tox-
ins. Finally, it removes excess of cytosolic dopamine (DA)
not stored in synaptic vesicles, hence protecting the neuron
from oxidative stress related to DA autoxidation (Bobela et
al., 2015). In particular, in the cytosol of dopaminergic neu-
rons, DA can be oxidized via iron-mediated catalysis and
then react with β-sheets-structured proteins to form a mel-
anin-protein complex. During the polymerization process,
the melanin-protein conjugate can also bind high amounts of
metals, especially iron. e resulting NM is taken up into au-
tophagic vacuoles that subsequently fuse with lysosomes; here
NM interacts with lipids and proteins already present, thus
forming the mature NM-containing organelles. erefore, by
analogy with peripheral melanins, NM could function in vivo
to attenuate the eects of damaging stimuli, but, unlike mela-
nin in skin and retina, NM is not present in SN dopaminergic
neurons of humans during foetal development or at birth,
but develops over the rst few decades of life (Fedorow et al.,
2005). Further, human foetal dopamine neurons, when im-
planted as a treatment into the striatum of patients with PD,
exhibit a precocious production of the pigment. is supports
the concept that factors involved in neuronal maturation are
important for the production of NM
(PDF) Odorants could elicit repair processes in melanizedneuronal and skin cells. Available from: https://www.researchgate.net/public...processes_in_melanizedneuronal_and_skin_cells [accessed Dec 10 2018].
