Neurotrophic Hormone Deficiency Theory
Overview
Neurotrophic Hormone Deficiency Theory was originally proposed by Appel et al., (1981) and is a modification to the Accelerated Aging Theory. This theory suggests that accelerated aging to particular neural areas is due to the presence of certain extrinsic factors1. The areas with these extrinsic factors experiencing accelerated aging (Degeneration) and are the common underlying cause of ALS, Parkinsonism, and Alzheimer’s Disease.
Commonalities of ALS, PD, and AD
To understand this theory, one must first understand the overlapping concepts of each of these diseases.
- All 3 diseases have changes in presynaptic neuronal input with secondary alterations of the target tissue1
- All 3 diseases sporadically occur later in life and the incidence increases with age1
- All 3 diseases have a familial form that occurs in 5-10% of patients1
- Heavy metal intoxication is a secondary cause of these diseases1
Presynaptic neuron changes + Target tissue alterations
Secondary Heavy Metal Onset
Accelerated Aging Theory
The Neurotrophic Hormone Deficiency Theory adds onto the accelerated aging theory. The accelerated aging theory refers to the idea that the relevant neural areas are experiencing accelerated aging, and therefore and degenerating faster1.
Advantages of the theory
- This theory explains why external causes such as viral nor abnormal factors have yet to be discovered for these 3 diseases.
- This theory helps to explain why there is a prevailing and consistent genetic incidence of ALS, PD, AD1
- Accelerated aging explains why disease incidence worsens with age1
- Lastly, this theory explains why external toxic factors such as heavy metal toxicity, trauma, viruses, infections, and vascular disease may increase the progression of these diseases
Disadvantages
Mechanism
Neurotrophic Hormone Deficiency Theory adds to the accelerated aging idea by suggesting that the areas that undergo accelerated aging is based on intrinsic neuronal properties1. Specifically, this theory hypothesizes that that each disease (ALS, PD, AD), experiences degeneration due to diminished availability of a specific neurotrophic hormone1. This neurotrophic hormone is normally released by the postsynaptic cell, taken up by the presynaptic terminal, and exerting its effect by retrograde transport up the presynaptic axon to the soma and nucleus1.
Practical examples of this theory
ALS
In ALS, if the muscle cells fail to release appropriate or enough motor neurotrophic hormones then there will be a failure in the anterior horn cells1. Gradually, this will result in a gradual cessation of anterior horn cell function, resulting in cell death1. In the upp motor neurons, Betz cells would result from diminished release of neurotrophic hormone from the target neurons1. The target neurons of Betz cells cannot be defined further due to lack of knowledge on the subject1.
PD
- Striatal cells are unable to provide the requisite dopamine (neurotrophic hormone)1
Alzheimer’s Disease
- Hippocampus and cortical cells fail to supple the cholinergic neurotrophic hormone1
Implications
If certain neural structures are degrading due to lack of a requisite neurotrophic hormone then restoring hormone levels may restore the failing presynpatic cells1.