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Neurodegenerative diseases include many disorders characterized by a progressive loss or dysfunction of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are all neurodegenerative diseases.
A common feature in most neurodegenerative diseases is the progressive accumulation of misfolded damaged proteins that are prone to aggregate and are involved in several cellular stress functions resulting in cell death. Although the mechanisms of action in neurodegenerative diseases are unclear, the potential underlying mechanisms can be divided into two categories. The first, unique to each neurodegenerative disease, is a trigger that will later initiate the cell death process of apoptosis. The second, which is thought to be universal among neurodegenerative diseases, is the consequential process which includes neuro-inflammation and death of neurons by apoptosis.
Pi3k/Akt signaling is a major pro-survival signaling pathway in many cells and is the most affected signaling pathway in the main neurodegenerative diseases.
Pi3k/Akt signaling is therefore a worthy target for drug development in a variety of neurodegenerative diseases.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a progressive paralytic disease characterized by selective degeneration and death of motor neurons in the brain and spinal cord that control voluntary muscle movement.
About 10% of ALS cases are familial, the remaining 90% of cases of ALS are sporadic and the cause of their disease is unknown. Key genes that are associated with increased ALS risk are known to affect the activity of the Akt pathway.
ALS is associated with the accumulation of misfolded proteins and insoluble inclusions such as TDP-43 in the sporadic disease and superoxide dismutase type-1 (SOD1) in some of the genetic disease cases. With the loss of motor neurons, the brain is no longer able to move or control voluntary muscle movement. As a result, muscles gradually atrophy and weaken to the point where patients become paralyzed and ultimately die.
ALS is the most common motor neuron system degenerative disease. The average disease onset age is approximately 50 years. The median reported survival from onset ranges from 24-48 months.
There is no cure for ALS. Riluzole and Edaravone, the only FDA-approved drugs for ALS treatment, extend survival by several months. Recent years have brought a wealth of new scientific understanding of this disease. This brings hope that a breakthrough in the treatment of ALS is closer than ever.
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