Neurodegenerative diseases

Generality

Neurodegenerative diseases are a set of pathologies characterized by an "irreversible and progressive loss of neuronal cells in certain areas of the brain.

The pathologies belonging to the group of neurodegenerative diseases are different and, for many of them, the causes of onset are still unclear.
In any case, it is believed that in the development of neurodegenerative diseases there is the involvement of several factors, which concur with each other in giving rise to the pathology. Among these factors, those of genetic and hereditary origin, and those of an environmental nature certainly stand out.
Neurodegenerative diseases can manifest themselves in different ways, depending on the area of ​​the brain affected by neuronal loss and depending on the type of neurons that are affected.
However, generally, all these pathologies have three points in common:

• Subtle and insidious onset, since in most cases the onset of the disease is asymptomatic and the symptoms appear only later, when the neuronal damage is quite extensive;
• Irreversible progression, since, unfortunately, there are still no treatments capable of definitively stopping neurodegenerative diseases;
• Purely symptomatic treatment.

Among the best known neurodegenerative diseases, we remember:

• Parkinson's disease;
• Alzheimer's disease;
• Amyotrophic lateral sclerosis;
• Huntington's chorea;
• Dementias.

The main characteristics of the aforementioned pathologies will be briefly illustrated below.

Parkinson's disease

Parkinson's disease is one of the best known neurodegenerative diseases.
This pathology is characterized by the degeneration of neurons located in the substantia nigra (substantia nigra) of the brain. More specifically, this degeneration determines an impairment of the ability to move, giving rise to symptoms, such as:

• Resting tremor
• Bradykinesia;
• Alteration of postural balance;
• Muscle stiffness.

In patients with Parkinson's disease there is a deficiency of the neurotransmitter dopamine; for this reason, among the active ingredients most used in the treatment of this neurodegenerative disease, there are:

• Dopamine precursors, such as levodopa;
• Dopaminergic agonists, such as pramipexole;
• Monoamine oxidase inhibitors, such as selegiline;
• Catechol-O-methyl transferase inhibitors, such as entacapone and tolcapone.

Alzheimer's disease

Alzheimer's disease is another of the best known neurodegenerative diseases.
It is characterized by the abnormal accumulation of proteins, such as β-amyloid, which forms plaques in the brain, and the protein tau, which causes the formation of neurofibrillary aggregates.
The neuronal loss that characterizes Alzheimer's disease causes serious alterations in cognitive functions and, in particular, affects the patient's short-term memory, learning ability and affective sphere.
The main drugs used in the treatment of Alzheimer's disease are:

• Acetylcholinesterase inhibitors, such as donepezil and rivastigmine;
• Memantine (a non-competitive antagonist for the glutamate receptor, a neurotransmitter thought to be involved in the neuronal damage that characterizes Alzheimer's disease);
• Vitamins with antioxidant action (such as vitamin E), which can be effective in counteracting the oxidative stress that is generated at the neuronal level in Alzheimer's patients.

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (also known by the acronym "ALS") is a neurodegenerative disease that affects the motor neurons of the central nervous system.
These neurons control the muscles; therefore, their damage can seriously compromise all movements (including breathing), giving rise to symptoms such as: difficulty walking, difficulty swallowing, speech difficulties, dyspnea and shortness of breath, up to respiratory failure.
Currently, the only active ingredient approved for the treatment of ALS is riluzole. This drug works by reducing the release of glutamate in the brain and spinal cord. In fact, it is believed that this particular neurotransmitter may be involved in the degeneration of motor neurons that characterizes this type of neurodegenerative disease.

Huntington's chorea

Huntington's chorea is an inherited neurodegenerative disease.

The disease in question arises due to the transmission of a mutated gene that codes for the huntingtin protein (or HTT). The protein encoded by this gene, therefore, is mutated and - even if the exact mechanisms by which this occurs are not known - it seems to be responsible for the degeneration of the neurons of the caudate nucleus that characterizes this disease.
Cognitive and motor skills are severely impaired in Huntington's disease patients. This impairment leads to symptoms such as: mood changes, memory loss, depression, difficulty walking, speech and swallowing.
Among the different drugs used in the symptomatic treatment of this neurodegenerative disease, we remember: anti-Parkinson drugs, antipsychotics and antidepressants.

Dementias

Dementias are a group of neurodegenerative diseases typical - but not exclusive - of old age. In this type of disease, the patient undergoes neuronal damage, which leads to a decline in cognitive functions.
There are several types of dementia and Alzheimer's disease is one of them. Among the other most common forms of dementia, we remember:

• Frontotemporal dementia;
• Lewy body dementia;
• Vascular dementia.

The symptomatology of dementia varies according to the area of ​​the brain in which neuronal damage occurs, therefore, it depends on the type of dementia that has affected the patient. Similarly, the type of treatment (however symptomatic) will also depend on the form of dementia from which the patient suffers.