Abstract
Autism is a neurodevelopmental disorder whose prevalence has increased
dramatically in the United States over the past two decades. It is
characterized by stereotyped behaviors and impairments in social
interaction and communication. In this paper, we present evidence that
autism can be viewed as a PIN1 deficiency syndrome. PIN1 (Peptidylprolyl
Cis/Trans Isomerase, NIMA-Interacting 1) is a peptidylprolyl cis/trans
isomerase, and it has widespread influences in biological organisms.
Broadly speaking, PIN1 deficiency is linked to many neurodegenerative
diseases, whereas PIN1 overexpression is linked to cancer. Death
associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the
hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly
linked to autism. It has recently been shown that glyphosate exposure to
rats inhibits melatonin synthesis due to increased glutamate release
from glial cells and increased expression of metabotropic glutamate
receptors. Glyphosate’s inhibition of melatonin leads to a reduction in
PIN1 availability in neurons. In this paper, we show that PIN1
deficiency can explain many of the unique morphological features of
autism, including increased dendritic spine density, missing or thin
corpus callosum and reduced bone density. We show how PIN1 deficiency
disrupts the functioning of powerful high level signaling molecules,
such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53.
Dysregulation of both of these proteins has been linked to autism.
Severe depletion of glutathione in the brain resulting from chronic
exposure to oxidative stressors and extracellular glutamate leads to
oxidation of the cysteine residue in PIN1, inactivating the protein and
further contributing to PIN1 deficiency. Impaired autophagy leads to
increased sensitivity of neurons to ferroptosis. Finally, we consider
evidence of the potential toxic effects of the mRNA SARS-CoV-2 vaccines
in the light of metabolic defects in autism, and we propose that
children with autism would be especially sensitive to damage from the
vaccines.