Introduction:
Iron is critical for the brain as it assists several vital brain functions. Therefore, healthy iron proportions in the brain are integral to ascertaining brain health and neurological functions. Any disparities in the iron proportion may call forth alarming health crises, warranting prompt medical care. Within the brain, iron atoms are engaged in several intricate processes.
How Is Iron Metabolized in the Brain?
Iron from the blood cuts across and navigates the blood-brain barrier (a delicate lamina that regulates and delimits the entry of blood elements into the brain). The conveyance of iron across the blood-brain barrier is aided by transferrin, which is a transport protein that complexes with the ferric iron (Fe3+), thus facilitating its transmission across the blood-brain barrier. This is how iron gains access to the brain. Within the brain cells, iron is gathered in a storage protein form called ferritin. Ferritin palliates the prospect of iron toxicity by segregating the excess iron within it, working like an iron reservoir.
When the brain cells signal for iron requirement, ferritin liberates the iron in the required proportions. Apart from ferritin, neurons and other glial cells (subsets of specialized cells in the brain that render support and shielding for neuronal functions), particularly microglia, astroglia, and oligodendrocytes, also enclose some proportions of iron within them. The iron acquired from the blood is then employed for instituting various brain functions, including:
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Neurotransmitter synthesis (formulation of the signal carriers that enable signal conveyance across the neurons).
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Myelin synthesis (synthesis of the protective sheath over the nerve axon).
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Mitochondrial respiration (energy generation process executed within the cell organelle mitochondria).
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DNA (deoxyribonucleic acid) synthesis (the generation and development of genetic components).
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Oxygen conveyance (conveyance of oxygen to the brain cells).
If the brain’s iron proportions overstep the requirement, then the excess is captured and detained within the ferritin. Likewise, when the iron-containing brain cells are knocked down or degraded, microglial cells immediately take up the cellular scraps and remnants and later express the iron, making it accessible for other cells to uptake and utilize. In this way, iron inside the brain is being reused or recycled, which upkeep the iron proportion within the brain, instituting iron homeostasis. However, if the iron proportion in the brain upscales, then the iron atoms are reverted back into the bloodstream. The iron exported from the brain’s cellular compartment to the blood is augmented by a transmembrane protein quoted under the denomination ferroportin. This is how iron is being utilized and processed within the brain.
Does Disturbed Iron Metabolism Bring out Neurodegeneration?
Disturbed or impeded iron metabolism could expedite and bring forth neurodegeneration. Neurodegeneration is the medical denomination for neuronal deterioration and atrophy. The harm to the neuron inflicted by neurodegeneration is mostly irrevocable, and hence, it could instigate permanent outcomes. The brain areas that are receptive to iron inflict the highest inclination for neurodegeneration. When the recycling and exporting of iron are hampered, it is reflected as an escalation in the iron proportion within the brain. The overstated iron proportions in the brain instigate oxidative stress (cellular harm inflicted by reactive oxygen species). Oxidative stress, over time, brings forth neurodegeneration. Iron overload can mute the mitochondrial (cell organelle) assignments, which in turn underscores the scope for neurodegeneration. However, the mechanism with which iron dyshomeostasis instigates discrete neurodegenerative disorders is not comprehended and explored completely. Various investigative studies are ongoing on the topic.
Which Are the Neurodegenerative Disorders Associated With Disrupted Iron Metabolism?
Some of the neurodegenerative disorders are known to be inflicted and driven by disrupted iron metabolism. Here are a few of such neurodegenerative conditions that could be invoked by iron dyshomeostasis.
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Alzheimer's Disease: Overstated iron proportions in the brain could be a factor that could augment Alzheimer's disease, where the individual encounters continuous and steady memory loss. In Alzheimer’s certain proteins assemble and build up in the brain cells, inflicting nerve degeneration. This protein aggregation is expedited by iron dyshomeostasis and thus deepens the prospects for Alzheimer’s disease.
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Parkinson's Disease: In Parkinson’s disease, one may encounter trouble with body balance and walking, slowed movements, fine tremors (shaking), and stiffening of body parts. It advances through stages or phases with progressive manifestations. The neuronal degeneration is inflicted on a specific brain area called basal ganglia (inner brain region, which governs critical brain functions like thinking, learning, controlling movements, and many more) that expedites the precipitation of Parkinson’s disease. Iron overloading is often elicited in Parkinson’s disease patients, which underscores the causal relationship linking iron dyshomeostasis and Parkinson’s disease.
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Multiple System Atrophy: A peculiar brain disorder that is prompted by neuronal damage and deterioration. Iron overload may induce and expedite oxidative stress, which in turn harms the nerves. The iron overload invokes aberrant gathering and agglomeration of iron within the brain tissue, inclusive of nerves. In multiple system atrophy (MSA), neuronal deteriorations are routinely elicited in specific brain areas like the brain stem, cerebellum, or basal ganglia; accordingly, the manifestations also reflect individual variances.
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Friedreich’s Ataxia: An aberration in the FXN (frataxin) gene gives rise to Friedreich’s ataxia. FXN gene encrypts for the frataxin, which is a mitochondrial protein that could regulate mitochondrial functions. In addition, it is imperative for modulating iron metabolism. Aberration or oddities in the FXN gene depreciate and mute frataxin production, which invokes derangements and disruptions in the iron metabolism.
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Amyotrophic Lateral Sclerosis: When the iron overload inflicts deterioration and mutilation of the motor neurons (nerves that govern and pilot the voluntary muscle functions), it could instigate amyotrophic lateral sclerosis. Occasional trips and slips, walking issues, withered and incapacitated legs and arms, fuzzy speech, and labored breathing are routinely confronted with amyotrophic lateral sclerosis. The overloaded iron gathers and agglomerates over the motor neurons, prompting and expediting their deterioration and harm. Certain studies have unveiled disrupted iron metabolism in amyotrophic lateral sclerosis patients.
Conclusion:
Various neurodegenerative diseases have projected causal connections with iron metabolism. Such pathophysiological linkage has underscored the pertinence of iron homeostasis and metabolic regulation in invoking neurodegeneration. Though many such neurodegenerative conditions crop up with aging, defective and undermined iron metabolism expedites and augments one’s propensity for neurodegeneration. Derangements or disablement in the iron’s metabolic pathways could gravitate to neuronal degeneration, and so does irrevocable harm to the nerves. These harms inflict disabilities: physical, mental, or both. Prompt medical interventions to stabilize and reinstate the iron homeostasis could palliate the scope and inclination for progressive nerve harm.
